MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Channels' source. Thu, 29 Dec 2011 10:41:40 +0100 http://www.medworm.com/index.php?rid=5527256&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22127232%26dopt%3DAbstract Authors: Bao M, Kanter EM, Huang RY, Maxeiner S, Frank M, Zhang Y, Schuessler RB, Smith TW, Townsend RR, Rohrs HW, Berthoud VM, Willecke K, Laing JG, Yamada KA Abstract Gap junction channels in ventricular myocardium are required for electrical and metabolic coupling between cardiac myocytes and for normal cardiac pump function. Although much is known about expression patterns and remodeling of cardiac connexin(Cx)43, little is known about the less abundant Cx45, which is required for embryonic development and viability, is downregulated in adult hearts, and is pathophysiologically upregulated in human end-stage heart failure. We applied quantitative immunoblotting and immunoprecipitation to native myocardial extracts, immunogold electron microscopy to cardiac tissue and membrane s... Channels journals http://www.medworm.com/rss/comments.php?id=5527256 Tue, 01 Nov 2011 04:00:00 +0100 5527256 http://www.medworm.com/index.php?rid=5527255&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172731%26dopt%3DAbstract Density of functional Ca ( 2+) release-activated Ca ( 2+) (CRAC) channels declines after T cell activation. Channels (Austin). 2011 Nov 1;5(6) Authors: Thakur P, Fomina AF Abstract CRAC channel-mediated Ca ( 2+)  entry plays a crucial role in T lymphocyte activation. Activated T cells display enhanced Ca ( 2+)  signaling compared with resting T cells; this is partially attributed to activation-induced upregulation of CRAC channel expression. Orai and Stim family genes encode CRAC channel structural elements and regulatory proteins, respectively, but studies of their expression in T cells have led to controversial results. We re-examined Orai and Stim gene expression in resting, activated, and Jurkat T cells. Levels of Orai1 transcripts, encoding the human T cell CRA... Channels journals http://www.medworm.com/rss/comments.php?id=5527255 Tue, 01 Nov 2011 04:00:00 +0100 5527255 http://www.medworm.com/index.php?rid=5527254&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22186697%26dopt%3DAbstract Authors: Marrus SB, Cuculich PS, Wang W, Nerbonne JM Abstract Andersen-Tawil syndrome is characterized by periodic paralysis, ventricular ectopy, and dysmorphic features. Approximately 60% of patients exhibit loss-of-function mutations in KCNJ2, which encodes the inwardly rectifying K+ channel pore forming subunit Kir2.1. Here, we report the identification of a novel KCNJ2 mutation (G211T), resulting in the amino acid substitution D71Y, in a patient presenting with signs and symptoms of Andersen-Tawil syndrome. The functional properties of the mutant subunit were characterized using voltage-clamp experiments on transiently transfected HEK-293 cells and neonatal mouse ventricular myocytes. Whole-cell current recordings of transfected HEK-293 cells demonstrated that the mutant protei... Channels journals http://www.medworm.com/rss/comments.php?id=5527254 Tue, 01 Nov 2011 04:00:00 +0100 5527254 http://www.medworm.com/index.php?rid=5414794&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22082832%26dopt%3DAbstract Authors: Deeb TZ, Lee HH, Walker JA, Davies PA, Moss SJ Abstract KCC2 comprises the major Cl- extruding mechanism in most adult neurons. Hyperpolarizing GABAergic transmission depends on KCC2 function. We recently demonstrated that glutamate reduces KCC2 function by a phosphorylation-dependent mechanism that leads to excitatory GABA responses. Here we investigated the methods by which to estimate changes in EGABA, as well as the processes that lead to depolarizing GABA responses and their effects on neuronal excitability. We demonstrated that current-clamp recordings of membrane potential responses to GABA can determine upper and lower limits of EGABA. We also further characterized depolarizing GABA responses, which both excited and inhibited neurons. Our analyses revealed that per... Channels journals http://www.medworm.com/rss/comments.php?id=5414794 Tue, 01 Nov 2011 04:00:00 +0100 5414794 http://www.medworm.com/index.php?rid=5414793&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22086202%26dopt%3DAbstract Authors: Zamponi GW PMID: 22086202 [PubMed - as supplied by publisher] (Source: Channels) Channels journals http://www.medworm.com/rss/comments.php?id=5414793 Tue, 01 Nov 2011 04:00:00 +0100 5414793 http://www.medworm.com/index.php?rid=5377413&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22020562%26dopt%3DAbstract Authors: Lipkind GM, Fozzard HA, Hanck DA Abstract Structure of the Ca channel open pore is unlikely to be the same as that of the K channel because Ca channels do not contain the hinge residues Gly or Pro. The Ca channel does not have a wide entry into the inner pore, as is found in K channels. First we sought to simulate the open state of the Ca channel by modeling forced opening of the KcsA channel using a procedure of restrained minimization with distance constraints at the level of the α-helical bundle, corresponding to segments Thr-107 - Val-115. This produced an intermediate open state, which was populated by amino acid residues of Ca channels and then successively optimized until the opening of the pore reached a diameter of about 11 Å, large enough to allow verapamil to ... Channels journals http://www.medworm.com/rss/comments.php?id=5377413 Tue, 01 Nov 2011 04:00:00 +0100 5377413 http://www.medworm.com/index.php?rid=5324507&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21993194%26dopt%3DAbstract Authors: Lapointe TK, Altier C Abstract Despite significant progress our understanding of the cellular and molecular mechanisms underlying sensory transduction and nociception, clinical pain management remains a considerable challenge in health care and basic research. The identification of the superfamily of transient receptor potential (TRP) cation channels, particularly TRPV1 and TRPA1, has shed light on the molecular basis of pain signaling during inflammatory conditions. TRPV1 and TRPA1 are considered as potential targets in the treatment of inflammatory pain because of their ability to be activated by nociceptive signals and sensitized by pro-inflammatory mediators. Notably, TRPA1 is expressed in visceral afferent neurons and is known to participate in inflammatory responses ... Channels journals http://www.medworm.com/rss/comments.php?id=5324507 Tue, 18 Oct 2011 10:10:32 +0100 5324507 http://www.medworm.com/index.php?rid=5324506&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21993195%26dopt%3DAbstract Authors: Braun AP Abstract Ever since Sydney Ringer's seminal observations in the late 1800's describing the essential role of Ca ( 2+) ions to support contraction in isolated frog hearts, a central focus in muscle physiology has been to understand the molecular mechanisms by which Ca ( 2+) elicits muscle contraction, how it enters the myocyte and how it is handled by the cellular proteins and organelles. One of the main entry routes for extracellular Ca ( 2+) into excitable tissues, such as muscle and nerve, is the voltage-gated Ca ( 2+) channel, which resides in the plasma membrane and opens in response to depolarizing stimulus. Voltage-gated Ca ( 2+) channels exist as a family comprised of three main subtypes denoted Cav 1, 2 and 3; Cav 1 is also commonly known as the L-type Ca ... Channels journals http://www.medworm.com/rss/comments.php?id=5324506 Tue, 18 Oct 2011 10:10:22 +0100 5324506 http://www.medworm.com/index.php?rid=5324505&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21993196%26dopt%3DAbstract Authors: Flucher BE, Tuluc P Abstract One of the earliest steps in the development of the neuromuscular junction (NMJ) is the pre-patterning of acetylcholine receptors (AChR) in the center of muscle fibers. This process has recently been proposed to depend on L-type calcium currents. But its feeble current properties make the skeletal muscle calcium channel (Cav 1.1) a poor candidate for this function. Independently a new Cav 1.1e splice variant with greatly distinct current properties has been described. But so far this channel lacked a function. Could this orphan channel be responsible for regulating AChR pre-patterning? Here we compare the properties of the two splice variants and argue that the newly discovered variant Cav 1.1e, is dominantly expressed at the proper time in de... Channels journals http://www.medworm.com/rss/comments.php?id=5324505 Tue, 18 Oct 2011 10:10:12 +0100 5324505 http://www.medworm.com/index.php?rid=5139512&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21829089%26dopt%3DAbstract Authors: Wang EE, Li H, Wang S, Chuang AY, Chuang HH Abstract Selective suppression of hyperactive sensory neurons is an attractive strategy for managing pathological pain. Blocking Na (+) channels to eliminate action potentials and desensitizing transduction channels can both reduce sensory neuron excitability. The novel synthetic vanilloid ligand cap-ET preserves agonist activation of intracellular Ca ( 2+) signals and large organic cation transport but loses effective electric current induction. Cap-ET can therefore be used to deliver the membrane impermeable Na (+) channel blocker QX-314 to substantially inhibit voltage-activated Na (+) currents. We explored, besides facilitating entry of organic cationic therapeutics, whether cap-ET can also produce receptor desensitization si... Channels journals http://www.medworm.com/rss/comments.php?id=5139512 Fri, 19 Aug 2011 12:12:19 +0100 5139512 http://www.medworm.com/index.php?rid=5139511&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21829090%26dopt%3DAbstract In this study, a mathematical model has been developed which incorporates many of the main biophysical principles which govern recordings of the resting potential of 'small cells'. Such a prototypical cell (approx. capacitance, 6pF; input resistance 5 GΩ) is representative of neonatal cardiac myocytes, and other cells in the cardiovascular system (endothelium, fibroblasts) and small cells in other tissues, e.g. bone (osteoclasts) articular joints (chondrocytes) and the pancreas (β cells). Two common experimental conditions have been examined: (1) when the background K+ conductance is linear; and (2) when this K+ conductance is highly nonlinear and shows pronounced inward rectification. In the case of a linear K+ conductance, the presence of a "leakage" current through the seal resistance... Channels journals http://www.medworm.com/rss/comments.php?id=5139511 Fri, 19 Aug 2011 12:12:13 +0100 5139511 http://www.medworm.com/index.php?rid=5139510&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21849820%26dopt%3DAbstract Authors: Machtens JP, Fahlke C, Kovermann P Abstract Excitatory amino acid transporters (EAATs) do not only mediate secondary-active glutamate uptake but also function as anion channels. We recently used macroscopic current recordings and noise analysis to determine unitary current amplitudes of anion channels associated with a neuronal EAAT isoform, EAAT4. We found that, at symmetrical NO3-, EAAT4 anion channels exhibit a single channel conductance of ~1 pS in the absence as well as in the presence of glutamate. These results indicate that glutamate increases EAAT4 anion currents by modifying exclusively open probabilities, however, leaves unitary current amplitudes unaffected. Noise analysis has been developed for ion channels with a single conductance state and limitations might... Channels journals http://www.medworm.com/rss/comments.php?id=5139510 Fri, 19 Aug 2011 12:12:06 +0100 5139510 http://www.medworm.com/index.php?rid=5092381&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21785269%26dopt%3DAbstract Authors: Brown MT, Korn C, Lüscher C The synaptic changes induced by initial drug exposure leave a trace on neural systems that can eventually manifest in compulsive drug-seeking behavior. A single injection of cocaine has been shown to induce a change in the AMPA receptor (AMPAR) subunit composition at glutamatergic synapses onto ventral tegmental area (VTA) dopamine (DA) neurons. This change is long-lasting (up to months following self-administration) and represents an important functional change at the synaptic level following cocaine use. We recently published findings that cocaine's action at the DA transporter (DAT) is necessary for the induction of AMPAR redistribution and that this can also be mimicked by selective DA neuron stimulation. The stimulation effect is depen... Channels journals http://www.medworm.com/rss/comments.php?id=5092381 Thu, 04 Aug 2011 08:15:24 +0100 5092381 http://www.medworm.com/index.php?rid=5041786&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21712647%26dopt%3DAbstract Authors: Zhao X, Yamazaki D, Kakizawa S, Pan Z, Takeshima H, Ma J Ca ( 2+) signaling in skeletal and cardiac muscles is a bi-directional process that involves cross-talk between signaling molecules in the sarcolemmal membrane and Ca ( 2+) release machinery in the intracellular organelles. Maintenance of a junctional membrane structure between the sarcolemmal membrane and the sarcoplasmic reticulum (SR) provides a framework for the conversion of action potential arrived at the sarcolemma into release of Ca ( 2+) from the SR, leading to activation of a variety of physiological processes. Activity-dependent changes in Ca ( 2+) storage inside the SR provides a retrograde signal for the activation of store-operated Ca ( 2+) channel (SOC) on the sarcolemmal membrane, which plays important ro... Channels journals http://www.medworm.com/rss/comments.php?id=5041786 Wed, 20 Jul 2011 21:15:30 +0100 5041786 http://www.medworm.com/index.php?rid=5041785&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21747233%26dopt%3DAbstract Authors: Ong HL, Ambudkar IS A rise in cytoplasmic [Ca ( 2+) ] due to store-operated Ca ( 2+) entry (SOCE) triggers a plethora of responses, both acute and long term. This leads to the important question of how this initial signal is decoded to regulate specific cellular functions. It is now clearly established that local [Ca ( 2+) ] at the site of SOCE can vary significantly from the global [Ca ( 2+) ] in the cytosol. Such Ca ( 2+) microdomains are generated by the assembly of key Ca ( 2+) signaling proteins within the domains. For example, GPCR, IP 3 receptors, TRPC3 channels, the plasma membrane Ca ( 2+) pump and the endoplasmic reticulum (ER) Ca ( 2+) pump have all been found to be assembled in a complex and all of them contribute to the Ca ( 2+) signal. Recent studies have reveale... Channels journals http://www.medworm.com/rss/comments.php?id=5041785 Wed, 20 Jul 2011 21:15:10 +0100 5041785 http://www.medworm.com/index.php?rid=4949569&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21654200%26dopt%3DAbstract Authors: Nakajo K, Kubo Y The KCNQ1 channel is a voltage-dependent potassium channel, which is widely expressed in various tissues of the human body including heart, inner ear, intestine, kidney and pancreas.  The ion channel properties of KCNQ1 change remarkably when auxiliary subunit KCNE proteins co-exist.  The mechanisms of KCNQ1 channel regulation by KCNE proteins are of longstanding interest but are still far from being fully understood.  The pore region (S5-S6 segments) of KCNQ1 is thought to be the main interaction site for KCNE proteins.  However, some recent reports showed that the voltage-sensing domain (S1-S4 segments) is critically involved in the regulation of KCNQ1 by KCNE proteins.  In addition, we recently re-examined the stoichiometry of the KCNQ1-KCNE1 complex a... Channels journals http://www.medworm.com/rss/comments.php?id=4949569 Tue, 21 Jun 2011 02:45:13 +0100 4949569 http://www.medworm.com/index.php?rid=4949568&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21654201%26dopt%3DAbstract Authors: Nishimune H Recent findings demonstrate that synaptic channels are directly involved in the formation and maintenance of synapses by interacting with synapse organizers. The synaptic channels on the pre- and postsynaptic membranes possess non-conducting roles in addition to their functional roles as ion-conducting channels required for synaptic transmission. For example, presynaptic voltage-dependent calcium channels link the target-derived synapse organizer laminin β2 to cytomatrix of the active zone and function as scaffolding proteins to organize the presynaptic active zones. Furthermore, postsynaptic δ2-type glutamate receptors organize the synapses by forming transsynaptic protein complexes with presynaptic neurexins through synapse organizer cerebellin 1 precursor prot... Channels journals http://www.medworm.com/rss/comments.php?id=4949568 Tue, 21 Jun 2011 02:45:08 +0100 4949568 http://www.medworm.com/index.php?rid=4636871&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21406958%26dopt%3DAbstract Authors: Garcia ZI, Bruhl A, Gonzales AL, Earley S The melastatin (M) transient receptor potential channel (TRP) channel TRPM4 is a critical regulator of vascular smooth muscle cell membrane potential and contractility. We recently reported that PKCδ activity influences smooth muscle cell excitability by promoting translocation of TRPM4 channel protein to the plasma membrane. Here we further investigate the relationship between membrane localization of TRPM4 protein and channel activity in native cerebral arterial myocytes. We find that TRPM4 immunolabeling is primarily located at or near the plasma membrane of freshly isolated cerebral artery smooth muscle cells. However, siRNA mediated downregulation of PKCδ or brief (15 min) inhibition of PKCδ activity with rottlerin causes TRPM4... Channels journals http://www.medworm.com/rss/comments.php?id=4636871 Sat, 26 Mar 2011 12:46:48 +0100 4636871 http://www.medworm.com/index.php?rid=4636870&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21406959%26dopt%3DAbstract Authors: Marger L, Mesirca P, Alig J, Torrente A, Dubel S, Engeland B, Kanani S, Fontanaud P, Striessnig J, Shin HS, Isbrandt D, Emke H, Nargeot J, Mangoni ME It is well established that Pacemaker activity of the sino-atrial node (SAN) initiates the heartbeat. However, the atrioventricular node (AVN) can generate viable pacemaker activity in case of SAN failure, but we have limited knowledge of the ionic bases of AVN automaticity. We characterized pacemaker activity and ionic currents in automatic myocytes of the mouse AVN. Pacemaking of AVN cells (AVNCs) was lower than that of SAN pacemaker cells (SANCs), both in control conditions and upon perfusion of isoproterenol (ISO). Block of INa by tetrodotoxin (TTX) or of ICa,L by isradipine abolished AVNCs pacemaker activity. TTX-resistant (... Channels journals http://www.medworm.com/rss/comments.php?id=4636870 Sat, 26 Mar 2011 12:46:38 +0100 4636870 http://www.medworm.com/index.php?rid=4636869&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21406960%26dopt%3DAbstract In conclusion, while Cav1.3 channels are required for automaticity, Cav 3.1 channels are important for maximal pacing rates of mouse AVNCs. HCN channels are important for basal AVNCs automaticity but do not appear to be determinant for β-adrenergic regulation. PMID: 21406960 [PubMed - as supplied by publisher] (Source: Channels) Channels journals http://www.medworm.com/rss/comments.php?id=4636869 Sat, 26 Mar 2011 12:46:29 +0100 4636869 http://www.medworm.com/index.php?rid=4636868&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21406961%26dopt%3DAbstract In this study, we examined the ability of this mutant CaV 1.1 channel (SkEIIIK) to conduct inward Na (+) current. When 150 mM Na (+) was present as the sole monovalent cation in the bath solution, dysgenic (CaV 1.1 null) myotubes expressing SkEIIIK displayed slowly-activating, non-inactivating, nifedipine-sensitive inward currents with a reversal potential (45.6 ± 2.5 mV) near that expected for Na (+) . Ca ( 2+) block of SkEIIIK-mediated Na (+) current was revealed by the substantial enhancement of Na (+) current amplitude after reduction of Ca ( 2+) in the external recording solution from 10 mM to near physiological 1 mM. Inward SkEIIIK-mediated currents were potentiated by either ±Bay K 8644 (10 mM) or 200-ms depolarizing prepulses to +90 mV. In contrast, outward monovalent current... Channels journals http://www.medworm.com/rss/comments.php?id=4636868 Sat, 26 Mar 2011 12:46:20 +0100 4636868 http://www.medworm.com/index.php?rid=4636867&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21406962%26dopt%3DAbstract In this study, planar lipid bilayer experiments demonstrated that the Sec61 complex is permeable to calcium ions. We also investigated whether silencing the SEC61A1 gene affected calcium leakage from the ER. Silencing the SEC61A1 gene using two different siRNAs in HeLa cells for 96 hours had little effect on cell growth and viability. However, calcium leakage from the ER was greatly decreased in the SEC61A1-silenced cells. Thus, the Sec61 complexes that are present in the ER membrane of nucleated cells form calcium leak channels that may play a crucial role in calcium homeostasis. PMID: 21406962 [PubMed - as supplied by publisher] (Source: Channels) Channels journals http://www.medworm.com/rss/comments.php?id=4636867 Sat, 26 Mar 2011 12:46:09 +0100 4636867 http://www.medworm.com/index.php?rid=4636866&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21406971%26dopt%3DAbstract Authors: Reichow SL, Korotkov KV, Gonen M, Sun J, Delarosa JR, Hol WG, Gonen T The type II secretion system (T2SS) is a large macromolecular complex spanning the inner and outer membranes of many Gram-negative bacteria. The T2SS is responsible for the secretion of virulence factors such as cholera toxin (CT) and heat-labile enterotoxin (LT) from Vibrio cholerae and enterotoxigenic Escherichia coli, respectively. CT and LT are closely related AB5 heterohexamers, composed of one A subunit and a B-pentamer. Both CT and LT are translocated, as folded protein complexes, from the periplasm across the outer membrane through the type II secretion channel, the secretin GspD. We recently published the 19 Å structure of the V. cholerae secretin (VcGspD) in its closed state and showed by SPR meas... Channels journals http://www.medworm.com/rss/comments.php?id=4636866 Sat, 26 Mar 2011 12:45:55 +0100 4636866 http://www.medworm.com/index.php?rid=4636865&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21406973%26dopt%3DAbstract Authors: Mahapatra S, Marcantoni A, Vandael DH, Striessnig J, Carbone E   Mouse and rat chromaffin cells (MCCs, RCCs) fire spontaneously at rest and their activity is mainly supported by the two L-type Ca ( 2+) channels expressed in these cells (Cav 1.2 and  Cav 1.3). Using  Cav 1.3 (-/-) KO MCCs we have shown that  Cav 1.3 possess all the prerequisites for carrying subthreshold currents that sustain low frequency cell firing near resting (0.5 to 2 Hz at -50 mV) ( 1) : low-threshold and steep voltage dependence of activation, slow and incomplete inactivation during pulses of several hundreds of milliseconds.  Cav 1.2 contributes also to pacemaking MCCs and possibly even Na (+) channels may participate in the firing of a small percentage of cells. We now show that at potentials nea... Channels journals http://www.medworm.com/rss/comments.php?id=4636865 Sat, 26 Mar 2011 12:45:42 +0100 4636865 http://www.medworm.com/index.php?rid=4636864&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21422811%26dopt%3DAbstract The "structurally minimal" isoform KChIP2d modulates recovery of Kv 4.3 N-terminal deletion mutant Δ 2-39. Channels (Austin). 2011 Jul 1;5(4) Authors: Hovind LJ, Campbell DL Mechanisms underlying Kv 4 (Shal type) potassium channel macroscopic (open state) inactivation and recovery are unknown, as are mechanisms by which KChIP2 isoforms modulate these two processes. In a recent study (Xenopus oocytes, 2 microelectrode voltage clamp) we demonstrated that: i) Partial deletion of the Kv 4.3 proximal N-terminal domain (Δ 2-39; deletes N-terminal amino acids 2-39) not only slowed macroscopic inactivation, but also slowed the net rate of recovery; and ii) Co-expression of KChIP2b significantly accelerated the rate Δ 2-39 recovery from inactivation. The latter effect demonstrated t... Channels journals http://www.medworm.com/rss/comments.php?id=4636864 Sat, 26 Mar 2011 12:45:28 +0100 4636864 http://www.medworm.com/index.php?rid=4461285&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21289476%26dopt%3DAbstract Authors: Wang J, Lanfranco MF, Gibb SL, Ron D We recently found that ethanol-induced long-term facilitation (LTF) of NMDAR activity is mediated by NR2B-NMDARs and is observed in the dorsomedial striatum (DMS) but not in the dorsolateral striatum (DLS).9 We also showed that repeated administration of ethanol causes a long-lasting increase in NMDAR activity in the DMS, resulting from ethanol-mediated Fyn phosphorylation of NR2B subunits.9 In this addendum, we report that the different sensitivity of NMDARs to ethanol between the DMS and DLS is not attributed to the abundance of synaptic NR2B-NMDARs or differences in Fyn levels. We further show that LTF is specific for NR2B-, but not NR2A-NMDARs, and that the duration of the in vivo ethanol-mediated increase in NMDAR activity is associate... Channels journals http://www.medworm.com/rss/comments.php?id=4461285 Fri, 11 Feb 2011 17:45:06 +0100 4461285 http://www.medworm.com/index.php?rid=4395377&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21224720%26dopt%3DAbstract Authors: Yamada H, Horita S, Suzuki M, Fujita T, Seki G The electrogenic Na (+) -HCO3 (-) cotransporter NBCe1 plays essential roles in the regulation of systemic and/or local pH. Homozygous inactivating mutations in NBCe1 cause proximal renal tubular acidosis associated with ocular abnormalities. We recently showed that defective membrane expression of NBCe1, caused by several mutations such as Delta65bp (S982NfsX4), is also associated with familial migraine. The Delta65bp mutant is quite unique in that it lacks a putative carbonic anhydrase (CA) II-binding domain but still shows an apparently normal transport activity in Xenopus oocytes. In this addendum, we show that the co-expression of CAII together with the wild-type NBCe1 or the Delta65bp mutant does not enhance the NBCe1 activit... Channels journals http://www.medworm.com/rss/comments.php?id=4395377 Tue, 25 Jan 2011 19:15:32 +0100 4395377 http://www.medworm.com/index.php?rid=4395376&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21224729%26dopt%3DAbstract In this study we describe a strain of transgenic mouse, G7-882, generated by incorporation into the mouse genome of human CaV1.2 α1C cDNA deprived of 3'-UTR to exclude transcription. We found that, in response to chronic infusion of isoproterenol, G7-882 develops dilated cardiomyopathy, a misleading "transgenic artifact" compatible with the expected function of the incorporated "correct" transgene. Specifically, using magnetic resonance imaging (MRI), we found that chronic β-adrenergic stimulation of G7-882 mice caused left ventricular hypertrophy and aggravated development of dilated cardiomyopathy, although no significant changes in the kinetics, density and voltage dependence of the calcium current were observed in G7-882 cardiomyocytes as compared to cells from wild type mice. This r... Channels journals http://www.medworm.com/rss/comments.php?id=4395376 Tue, 25 Jan 2011 19:15:25 +0100 4395376 http://www.medworm.com/index.php?rid=4395375&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21239886%26dopt%3DAbstract We examined the binding of the F loop (P1107 A1121) in SPRY2 to the ASI/basic region in RyR1 (T3471-G3500, containing both alternatively spliced (ASI) residues and neighboring basic amino acids). We then investigated the possible influence of this interaction on excitation contraction (EC) coupling. A peptide with the F loop sequence and an antibody to the SPRY2 domain each enhanced RyR1 activity at low concentrations and inhibited at higher concentrations. A peptide containing the ASI/basic sequence bound to SPRY2 and binding decreased ~10-fold following mutation or structural disruption of the basic residues. Binding was abolished by mutation of three critical acidic F loop residues. Together these results suggest that the ASI/basic and SPRY2 domains interact in an F loop regulatory modu... Channels journals http://www.medworm.com/rss/comments.php?id=4395375 Tue, 25 Jan 2011 19:15:19 +0100 4395375 http://www.medworm.com/index.php?rid=4395374&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21239887%26dopt%3DAbstract Authors: Hendrickson LM, Gardner P, Tapper AR Recently, we investigated the molecular mechanisms of the smoking cessation drug varenicline, a nicotinic acetylcholine receptor (nAChR) partial agonist, in its ability to decrease voluntary ethanol intake in mice. Previous to our study, other labs had shown that this drug can decrease ethanol consumption and seeking in rat models of ethanol intake. Although varenicline was designed to be a high affinity partial agonist of nAChRs containing the α4 and β2 subunits (designated as α4β2*), at higher concentrations it can also act upon α3β2*, α6*, α3β4* and α7 nAChRs. Therefore, to further elucidate the nAChR subtype responsible for varenicline-induced reduction of ethanol consumption, we utilized a pharmacological approach in combinat... Channels journals http://www.medworm.com/rss/comments.php?id=4395374 Tue, 25 Jan 2011 19:15:10 +0100 4395374 http://www.medworm.com/index.php?rid=4318997&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21150292%26dopt%3DAbstract Authors: Tottene A, Urbani A, Pietrobon D Gain-of-function mutations in CaV2.1 (P/Q-type) Ca (2+) channels cause familial hemiplegic migraine type 1 (FHM1), a subtype of migraine with aura. Knockin (KI) mice carrying FHM1 mutations show increased neuronal P/Q-type current and facilitation of induction and propagation of cortical spreading depression (CSD), the phenomenon that underlies migraine aura and may activate migraine headache mechanisms. We recently studied cortical neurotransmission in neuronal microcultures and brain slices of FHM1 KI mice, and showed i. gain-of-function of excitatory neurotransmission, due to increased action potential-evoked Ca (2+) influx and increased probability of glutamate release at pyramidal cell synapses, but unaltered inhibitory neurotransmission a... Channels journals http://www.medworm.com/rss/comments.php?id=4318997 Fri, 07 Jan 2011 12:47:16 +0100 4318997 http://www.medworm.com/index.php?rid=4318996&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21150293%26dopt%3DAbstract Authors: Liao Z, St Clair JR, Larson ED, Proenza C The funny current, If, in sinoatrial myocytes is thought to contribute to the sympathetic fight-or-flight increase in heart rate. If is produced by hyperpolarization-activated cyclic nucleotide sensitive-4 (HCN4) channels, and it is widely believed that sympathetic regulation of If occurs via direct binding of cAMP to HCN4, independent of phosphorylation. However, we have recently shown that Protein Kinase A (PKA) activity is required for sympathetic regulation of If, and that PKA can directly phosphorylate HCN4. (1) In the present study, we examined the effects of a myristoylated PKA inhibitory peptide (myr-PKI) on If in mouse sinoatrial myocytes. We found that myr-PKI and another myristoylated peptide potently and specifically potent... Channels journals http://www.medworm.com/rss/comments.php?id=4318996 Fri, 07 Jan 2011 12:47:12 +0100 4318996 http://www.medworm.com/index.php?rid=4318995&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21150294%26dopt%3DAbstract Authors: Schlichter LC, Mertens T, Liu B Microglia have a swelling-activated Cl- current (which we call IClswell), and while some of its biophysical properties and functional roles have been elucidated, its molecular identity is unknown. To relate this current to cell functions and determine whether it is regulated by mechanisms other than cell swelling, it is important to establish both biophysical and pharmacological fingerprints. Here, we used rat microglia and a cell line derived from them (MLS-9) to study biophysical, regulatory and pharmacological properties of IClswell. The whole-cell current was activated in response to a hypo-osmotic bath solution, but not by voltage, and was time-independent during long voltage steps. The halide selectivity sequence was I->Br->Cl- (Eise... Channels journals http://www.medworm.com/rss/comments.php?id=4318995 Fri, 07 Jan 2011 12:47:09 +0100 4318995 http://www.medworm.com/index.php?rid=4318994&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21150295%26dopt%3DAbstract Authors: Yuchi Z, Van Petegem F Ryanodine receptors (RyRs) are calcium release channels found in the membrane of the endoplasmic reticulum (ER). We recently described the crystal structure of the RyR1 N-terminal disease hot spot. It is built up by three domains that show clear structural homology with the inositol-1,4,5-triphosphate (IP3) binding core and suppressor domain of IP3 receptors (IP3Rs) . Here we analyze the structural features of the domains in both calcium release channels, and propose a model for the closed state of the IP3R N-terminal region. This model explains the effect of the suppressor domain on the affinity for IP3 and is supported by mutational studies performed previously. We propose a mechanism whereby opening of both RyR and IP3R is allosterically coupled to a ... Channels journals http://www.medworm.com/rss/comments.php?id=4318994 Fri, 07 Jan 2011 12:47:06 +0100 4318994 http://www.medworm.com/index.php?rid=4215401&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21099342%26dopt%3DAbstract Authors: Groome JR, Lehmann-Horn F, Holzherr BD The role of sodium channel closed-state fast inactivation in membrane excitability is not well understood. We compared open- and closed-state fast inactivation, and the gating charge immobilized during these transitions, in skeletal muscle channel hNa(V)1.4. A significant fraction of total charge movement and its immobilization occurred in the absence of channel opening. Simulated action potentials in skeletal muscle fibers were attenuated when pre-conditioned by subthreshold depolarization. Anthopleurin A, a site-3 toxin that inhibits gating charge associated with the movement of DIVS4, was used to assess the role of this voltage sensor in closed-state fast inactivation. Anthopleurin elicited opposing effects on the gating mode, kinetics... Channels journals http://www.medworm.com/rss/comments.php?id=4215401 Wed, 01 Dec 2010 13:00:09 +0100 4215401 http://www.medworm.com/index.php?rid=4087903&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20953143%26dopt%3DAbstract Authors: Flynn R, Zamponi G The RGK family of proteins, small GTPases of the Ras superfamily, are known to regulate calcium currents. It is commonly thought that this is due to an interaction with the Ca(V)β subunit, however, the mechanism of this inhibition is unclear. There have been conflicting reports of whether RGK proteins can affect channel trafficking or whether they reduce calcium currents by interacting with channels at the membrane. In the last year, several studies have emerged which explore the intricacies of RGK protein interaction with the channel itself and the importance of the Ca(V)β subunit for this interaction, in addition to providing some tantalizing suggestions for the mechanism by which RGK proteins reduce or eliminate calcium currents. In this review, we pres... Channels journals http://www.medworm.com/rss/comments.php?id=4087903 Fri, 22 Oct 2010 19:15:13 +0100 4087903 http://www.medworm.com/index.php?rid=4087902&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20953144%26dopt%3DAbstract Authors: García-Caballero A, Ishmael SS, Dang Y, Gillie D, Bond JS, Milgram SL, Stutts MJ The Epithelial Na(+) Channel (ENaC) is an apical heteromeric channel that mediates Na(+) entry into epithelial cells from the luminal cell surface. ENaC is activated by proteases that interact with the channel during biosynthesis or at the extracellular surface. Meprins are cell surface and secreted metalloproteinases of the kidney and intestine. We discovered by affinity chromatography that meprins bind γ-ENaC, a subunit of the ENaC hetero-oligomer. The physical interaction involves NH(2)-terminal cytoplasmic residues 37-54 of γ-ENaC, containing a critical gating domain immediately before the first transmembrane domain, and the cytoplasmic COOH-terminal tail of meprin β (residues 679-704). Th... Channels journals http://www.medworm.com/rss/comments.php?id=4087902 Fri, 22 Oct 2010 19:15:09 +0100 4087902 http://www.medworm.com/index.php?rid=4087901&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20953145%26dopt%3DAbstract Authors: Renna MD, Sangaletti R, Bossi E, Cherubino F, Kottra G, Peres A Electrophysiological and biophysical analyses were used to compare the partial and complete transport cycles of the intestinal oligopeptide transporter PepT1 among three species (seabass, zebrafish and rabbit). On the whole, the presteady-state currents of the fish transporters were similar to each other. Rabbit PepT1 differed from the fish transporters by having slower-decaying currents, and the charge vs. potential (Q/V) and time constant vs. potential (Τ/V) curves shifted to more positive potentials. All of the isoforms were similarly affected by external pH, showing acidity-induced slowing of the transients and positive shifts in the Q/V and Τ/V curves. Analysis of the pH-dependence of the unidirectional rat... Channels journals http://www.medworm.com/rss/comments.php?id=4087901 Fri, 22 Oct 2010 19:15:06 +0100 4087901 http://www.medworm.com/index.php?rid=4061216&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20935476%26dopt%3DAbstract Authors: Weiss N PMID: 20935476 [PubMed - as supplied by publisher] (Source: Channels) Channels journals http://www.medworm.com/rss/comments.php?id=4061216 Wed, 13 Oct 2010 09:35:08 +0100 4061216 http://www.medworm.com/index.php?rid=3962073&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20818184%26dopt%3DAbstract Authors: Thompson JL, Mignen O, Shuttleworth TJ Although highly selective Ca(2+) entry pathways play a critical role in agonist-activated Ca(2+) signals in non-excitable cells, only with the recent discovery of the Orai proteins have the first insights into the molecular nature of these pathways been possible. To date, just two such highly Ca(2+)-selective "Orai channels" have been identified in native cells-the store-operated CRAC channels and the store-independent, arachidonic acid-activated ARC channels. Studies have shown that the functional CRAC channel pore is formed by a tetrameric arrangement of Orai1 subunits, whilst a heteropentamer of three Orai1 subunits and two Orai3 subunits forms the functional ARC channel pore. Importantly, this inclusion of Orai3 subunits in the ARC ch... Channels journals http://www.medworm.com/rss/comments.php?id=3962073 Mon, 13 Sep 2010 11:33:14 +0100 3962073 http://www.medworm.com/index.php?rid=3863450&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20699637%26dopt%3DAbstract Authors: Ahrendt E, Braun JE PMID: 20699637 [PubMed - as supplied by publisher] (Source: Channels) Channels journals http://www.medworm.com/rss/comments.php?id=3863450 Sat, 14 Aug 2010 06:18:20 +0100 3863450 http://www.medworm.com/index.php?rid=3863449&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20699644%26dopt%3DAbstract Authors: David LS, Garcia E, Cain SM, Thau EM, Tyson JR, Snutch TP Low voltage-activated T-type calcium (Ca) channels contribute to the normal development of the heart and are also implicated in pathophysiological states such as cardiac hypertrophy. Functionally distinct T-type Ca channel isoforms can be generated by alternative splicing from each of three different T-type genes (Ca(V)3.1, Ca(V)3.2, Ca(V)3.3), although it remains to be described whether specific splice variants are associated with developmental states and pathological conditions. We aimed to identify and functionally characterize Ca(V)3.2 T-type Ca channel alternatively spliced variants from newborn animals and to compare with adult normotensive and spontaneously hypertensive rats (SHR). DNA sequence analysis of full-l... Channels journals http://www.medworm.com/rss/comments.php?id=3863449 Sat, 14 Aug 2010 06:18:16 +0100 3863449 http://www.medworm.com/index.php?rid=3863448&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20699649%26dopt%3DAbstract Authors: Koeberle PD, Schlichter LC Retinal ganglion cell (RGC) degeneration is an important cause of visual impairment, and results in part from microglia-mediated inflammation. Numerous experimental studies have focused on identifying drug targets to rescue these neurons. We recently showed that K(V)1.1 and K(V)1.3 channels are expressed in adult rat RGCs and that siRNA-mediated knockdown of either channel reduces RGC death after optic nerve transection. Earlier we found that K(V)1.3 channels also contribute to microglial activation and neurotoxicity; raising the possibility that these channels contribute to neurodegeneration through direct roles in RGCs and through inflammatory mechanisms. Here, RGC survival was increased by combined siRNA-mediated knockdown of K(V)1.1 and K(V)1.3 i... Channels journals http://www.medworm.com/rss/comments.php?id=3863448 Sat, 14 Aug 2010 06:18:13 +0100 3863448 http://www.medworm.com/index.php?rid=3863447&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20699650%26dopt%3DAbstract Authors: Kurup P, Zhang Y, Venkitaramani DV, Xu J, Lombroso PJ Amyloid beta (Abeta), the putative causative agent in Alzheimer disease, is known to affect glutamate receptor trafficking. Previous studies have shown that Abeta downregulates the surface expression of N-methyl D-aspartate type glutamate receptors (NMDARs) by the activation of STriatal-Enriched protein tyrosine Phosphatase 61 (STEP(61)). More recent findings confirm that STEP(61) plays an important role in Abeta-induced NMDAR endocytosis. STEP levels are elevated in human AD prefrontal cortex and in the cortex of several AD mouse models. The increase in STEP(61) levels and activity contribute to the removal of GluN1/GluN2B receptor complexes from the neuronal surface membranes. The elevation of STEP(61) is due to disruptio... Channels journals http://www.medworm.com/rss/comments.php?id=3863447 Sat, 14 Aug 2010 06:18:09 +0100 3863447 http://www.medworm.com/index.php?rid=3863446&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20699659%26dopt%3DAbstract In this study we have taken advantage of the acidic intracellular environment of S. cerevisiae and used a K(+)-auxotrophic strain to screen for mutants of Kir1.1 with impaired pH-sensitivity. In addition to the previously identified K80M mutation, this unbiased screening approach identified a novel mutation (S172T) in the second transmembrane domain (TM2) that also produces a marked reduction in pH-sensitivity through destabilization of the closed-state. However, despite this extensive mutagenic approach, no mutations could be identified which removed channel pH-sensitivity or which were likely to act as a separate H(+)-sensor unique to the pH-sensitive Kir channels. In order to explain these results we propose a model in which the pH-sensing mechanism is part of an intrinsic gating mechan... Channels journals http://www.medworm.com/rss/comments.php?id=3863446 Sat, 14 Aug 2010 06:18:06 +0100 3863446 http://www.medworm.com/index.php?rid=3633691&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20519930%26dopt%3DAbstract We report here our efforts to understand this apparent contradiction. We determined the Ca(2+) dependence of IK1 and BK channels in mouse parotid acinar cells. IK1 channels activated with an apparent Ca(2+) affinity of about 350 nM and a Hill coefficient near 3. Native parotid BK channels activated at similar Ca(2+) levels unlike the BK channels in other cell types. Since the parotid BK channel is encoded by an uncommon splice variant, we examined this clone in a heterologous expression system. In contrast to the native parotid channel, activation of this expressed "parSlo" channel required very high levels of Ca(2+). In order to understand the functional basis for the special properties of the native channels, we analyzed the parotid BK channel in the context of the Horrigan-Aldrich model... Channels journals http://www.medworm.com/rss/comments.php?id=3633691 Sun, 06 Jun 2010 18:45:05 +0100 3633691 http://www.medworm.com/index.php?rid=3596636&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20495360%26dopt%3DAbstract Authors: Cohen-Kutner M, Nachmanni D, Atlas D It is well established that syntaxin 1A (Sx1A), SNAP-25 and synaptotagmin (Syt1) either alone or in combination, modify the kinetic properties of voltage-gated Ca(2+) channels (VGCCs). The interaction interface resides mainly at the cytosolic II-III domain of the alpha1 subunit of the channels, while Sx1A interacts with the channel also via two highly conserved cysteine residues at the transmembrane domain. In the present study, we characterized Ca(2+)-independent coupling of the human neuronal P/Q-type calcium channel (Ca(V)2.1) with Sx1A, SNAP-25, Syt1 and synaptobrevin (VAMP) in BAPTA-injected Xenopus oocytes. The co-expression of Ca(V)2.1 with Sx1A, SNAP-25 and Syt1, produced a multiprotein complex with distinctive kinetic properties an... Channels journals http://www.medworm.com/rss/comments.php?id=3596636 Wed, 26 May 2010 12:18:06 +0100 3596636 http://www.medworm.com/index.php?rid=3362612&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20224299%26dopt%3DAbstract Authors: Sager C, Tapken D, Hollmann M AMPA receptors mediate the majority of fast synaptic transmission in the central nervous system and are therefore among the most intensively studied ligand-gated ion channels over the last decades. However, the recent discovery that native AMPA receptor complexes contain auxiliary subunits classified as transmembrane AMPA receptor regulatory proteins (TARPs) was quite a surprise and dramatically changed the field of AMPA receptor research. TARPs regulate trafficking as well as synaptic localization of AMPA receptors, and alter their pharmacological and biophysical properties, generally resulting in strongly elevated receptor-mediated currents. Thus, the association of AMPA receptors with TARPs increases receptor heterogeneity and diversity of post... Channels journals http://www.medworm.com/rss/comments.php?id=3362612 Sat, 13 Mar 2010 17:24:06 +0100 3362612 http://www.medworm.com/index.php?rid=3255076&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20139710%26dopt%3DAbstract Authors: Barry PH, Sugiharto S, Lewis TM, Moorhouse AJ The functional role of ion channels, which allow counterion permeation, depends critically on their relative anion-cation selectivity. From whole-cell patch clamp reversal potential measurements under dilution potential conditions, we have already shown that anion-cation permeabilities of anion-selective wild-type (WT) and mutant (with larger pore diameter) glycine receptor (GlyR) channels in the presence of Li(+), Na(+) and Cs(+) counterions, were inversely correlated with the equivalent hydration diameter of the counterion, with chloride-cation permeability increasing as counterion equivalent hydration diameter increased with respect to the channel minimum pore diameter. Corrected for liquid junction potentials (LJPs; using ion a... Channels journals http://www.medworm.com/rss/comments.php?id=3255076 Tue, 09 Feb 2010 21:24:06 +0100 3255076 http://www.medworm.com/index.php?rid=3031935&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19934647%26dopt%3DAbstract Authors: Kussius CL, Popescu AM, Popescu GK The mechanism by which ligand binding at extracellular receptor domains gates a transmembrane ion-conducting pore is insufficiently understood. Examining a channel's activation reaction in the presence of agonists with distinct efficacies may inform this issue and may help identify agonist-dependent transitions. We have recently applied this approach to NMDA receptors composed of GluN1 and GluN2A subunits. Based on our results with several subunit-specific partial agonists we concluded that agonist effects were distributed over several of the multiple transitions that make up NMDA receptor gating and that these changes were subunit independent. Here we examine an additional GluN2A partial agonist, 4-fluoro-D, L-glutamic acid, and we summarize... Channels journals http://www.medworm.com/rss/comments.php?id=3031935 Fri, 27 Nov 2009 14:08:05 +0100 3031935 http://www.medworm.com/index.php?rid=3015666&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19923917%26dopt%3DAbstract Authors: Rosenhouse-Dantsker A, Leal-Pinto E, Logothetis DE, Levitan I Kir channels are important in setting the resting membrane potential and modulating membrane excitability. A common feature of Kir2 channels and several other ion channels that has emerged in recent years is that they are regulated by cholesterol, a major lipid component of the plasma membrane whose excess is associated with multiple pathological conditions. Yet, the mechanism by which cholesterol affects channel function is not clear. We have recently shown that the sensitivity of Kir2 channels to cholesterol depends on residues in the CD loop of the cytosolic domain of the channels with one of the mutations, L222I, abrogating cholesterol sensitivity of the channels completely. Here we show that in addition to Kir2... Channels journals http://www.medworm.com/rss/comments.php?id=3015666 Sun, 22 Nov 2009 00:42:05 +0100 3015666 http://www.medworm.com/index.php?rid=2985245&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19901534%26dopt%3DAbstract Authors: Kline CF, Hund TJ, Mohler PJ K(ATP) channels play critical roles in many cellular functions by coupling cell metabolic status to electrical activity. First discovered in cardiomyocytes,(1) K(ATP) channels (comprised of Kir6.x and SUR subunits) have since been found in many other tissues, including pancreatic beta cells, skeletal muscle, smooth muscle, brain, pituitary and kidney. By linking cellular metabolic state with membrane potential, K(ATP) channels are able to regulate a number of cellular functions such as hormone secretion, vascular tone and excitability. Specifically, a reduction in metabolism causes a decrease in the ATP:ADP ratio, opening of K(ATP) channels, K(+) efflux, membrane hyperpolarization, and suppression of electrical activity. Conversely, increased cellu... Channels journals http://www.medworm.com/rss/comments.php?id=2985245 Thu, 12 Nov 2009 18:38:07 +0100 2985245 http://www.medworm.com/index.php?rid=2985244&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19901547%26dopt%3DAbstract Authors: Jerng HH, Dougherty K, Covarrubias M, Pfaffinger PJ The somatodendritic subthreshold A-type K(+) current in neurons (I(SA)) depends on its kinetic and voltage-dependent properties to regulate membrane excitability, action potential repetitive firing, and signal integration. Key functional properties of the K(V)4 channel complex underlying I(SA) are determined by dipeptidyl peptidase-like proteins known as dipeptidyl peptidase 6 (DPP6) and dipeptidyl peptidase 10 (DPP10). Among the multiple known DPP10 isoforms with alternative N-terminal sequences, DPP10a confers exceptionally fast inactivation to K(V)4.2 channels. To elucidate the molecular basis of this fast inactivation, we investigated the structure-function relationship of the DPP10a N-terminal region and its interaction ... Channels journals http://www.medworm.com/rss/comments.php?id=2985244 Thu, 12 Nov 2009 18:38:04 +0100 2985244 http://www.medworm.com/index.php?rid=2871391&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19806008%26dopt%3DAbstract In this report we further elucidate the role of the actin cytoskeleton in this process using pharmacological tools to disrupt or stabilize actin filaments and to prevent protein trafficking and vesicle recycling. Disruption of the cytoskeleton did not affect the basal activity of alpha(1H), but did eliminate its modulation by KLHL1. In contrast, actin-F stabilization on its own increased basal alpha(1H) activity similar to KLHL1 but without synergy in its presence, suggesting KLHL1 requires actin-polymerization to increase alpha(1H) currents. Noise analysis revealed that actin polymerization induced an increase in N and P(o), in contrast to increased N in the presence of KLHL1. Interestingly, pharmacological or genetic disruption of endosomal recycling eliminated the increase in channel nu... Channels journals http://www.medworm.com/rss/comments.php?id=2871391 Thu, 08 Oct 2009 11:20:16 +0100 2871391 http://www.medworm.com/index.php?rid=2871390&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19806011%26dopt%3DAbstract Authors: Benton MD, Raman IM Purkinje neurons fire spontaneous action potentials at approximately 50 spikes/sec and generate more than 100 spikes/sec during cerebellum-mediated behaviors. Many voltage-gated channels, including Ca channels, can inactivate and/or facilitate with repeated stimulation, raising the question of how these channels respond to regular, rapid trains of depolarizations. To test whether Ca currents are modulated during firing, we recorded voltage-clamped Ca currents, predominantly carried by P-type Ca channels, from acutely dissociated mouse Purkinje neurons at 30-33 degrees C (1 mM Ca). With 0.5 mM intracellular EGTA, 1-second trains of either spontaneous action potential waveforms or brief depolarizing steps at 50 Hz evoked Ca tail currents that were stable, rem... Channels journals http://www.medworm.com/rss/comments.php?id=2871390 Thu, 08 Oct 2009 11:20:13 +0100 2871390 http://www.medworm.com/index.php?rid=2871389&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19806027%26dopt%3DAbstract Authors: Skerritt MR, Campbell DL Effects of neutralizing individual negatively charged (acidic [E,D]) and innermost positively charged (basic [K,R]) residues in transmembrane segments S2 (D230Q, E240Q), S3 (D263Q) and S4 (K299A/Q, R302A/Q) of the K(V)4.3 putative voltage sensing domain (VSD) were determined. S2 D230Q generated large macroscopic currents, depolarized steady-state activation ("a(4)") and isochronal (1 sec) inactivation ("i") relationships, and significantly accelerated kinetics of deactivation and recovery (from both macroscopic and closed state inactivation [CSI]). D230Q thus stabilized non-inactivated closed states. These effects were attributable to structural perturbations, and indicated D230 is not primarily involved in voltage sensing. Both S2 E240Q and S3 D263Q f... Channels journals http://www.medworm.com/rss/comments.php?id=2871389 Thu, 08 Oct 2009 11:20:08 +0100 2871389 http://www.medworm.com/index.php?rid=2871388&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19806033%26dopt%3DAbstract Authors: Takeuchi A, Reyes N, Artigas P, Gadsby DC The Na(+),K(+)-ATPase pump achieves thermodynamically uphill exchange of cytoplasmic Na(+) ions for extracellular K(+) ions by using ATP-mediated phosphorylation, followed by autodephosphorylation, to power conformational changes that allow ion access to the pump's binding sites from only one side of the membrane at a time. Formally, the pump behaves like an ion channel with two tightly coupled gates that are constrained to open and close alternately. The marine agent palytoxin disrupts this coupling, allowing both gates to sometimes be open, so temporarily transforming a pump into an ion channel. We made a cysteine scan of Na(+),K(+)-ATPase transmembrane (TM) segments TM1 to TM6, and used recordings of Na(+) current flow through palyt... Channels journals http://www.medworm.com/rss/comments.php?id=2871388 Thu, 08 Oct 2009 11:20:05 +0100 2871388 http://www.medworm.com/index.php?rid=2745784&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19713736%26dopt%3DAbstract Authors: Barrow AJ, Wu SM In addition to the HCN1 channels that mediate the h current, the Kx current also performs signal filtering in rod photoreceptors. This current is known to be mediated by potassium channels and has similarities to the neuronal M current and EAG potassium channels. Although it is known that in filtering the light response of rods, I(h) and I(Kx) undergo complementary conductance changes, the qualities and significance of these changes are not clear. Here we present an analysis demonstrating the filtering effect of HCN1 channels in salamander rods when I(Kx) is blocked, and a simulation of the rod light response showing the magnitude and time course of the conductance changes by both currents. From this analysis, we propose that the purpose of opposing conductanc... Channels journals http://www.medworm.com/rss/comments.php?id=2745784 Sun, 30 Aug 2009 20:38:17 +0100 2745784 http://www.medworm.com/index.php?rid=2745783&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19713738%26dopt%3DAbstract Authors: Benmocha A, Almagor L, Oz S, Hirsch JA, Dascal N Interaction of calmodulin (CaM) with the C-terminus (CT) of the L-type Ca(V)1.2 channel is crucial for Ca(2+)-dependent inactivation (CDI). CaM also binds to the N-terminus (NT), and a CaM-formed "bridge" between CT and NT has been proposed to control CDI. We characterized the interaction of CaM with its NT-binding peptide. Binding is Ca(2+)-dependent with an affinity of 0.6 muM. Mutations in NT of Ca(V)1.2 that abolished the binding of CaM only slightly weakened the CDI but also accelerated the VDI. CaM did not foster an interaction between the CaM-binding peptides of NT and CT. Thus, the role of CaM's interaction with the Ca(V)1.2 NT remains to be determined. PMID: 19713738 [PubMed - as supplied by publisher] (Source: Chan... Channels journals http://www.medworm.com/rss/comments.php?id=2745783 Sun, 30 Aug 2009 20:38:15 +0100 2745783 http://www.medworm.com/index.php?rid=2745782&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19713739%26dopt%3DAbstract Authors: Benfenati V, Caprini M, Nicchia GP, Rossi A, Dovizio M, Cervetto C, Nobile M, Ferroni S Accumulating evidence indicate that the gap-junction inhibitor carbenoxolone (CBX) regulates neuronal synchronization, depresses epileptiform activity and has a neuroprotective action. These CBX effects do not depend solely on its ability to inhibit gap junction channels formed by connexins (Cx), but the underlying mechanisms remain to be elucidated. Here we addressed the questions whether CBX modulates volume-regulated anion channels (VRAC) involved in the regulatory volume decrease and regulates the associated release of excitatory amino acids in cultured rat cortical astrocytes. We found that CBX inhibits VRAC conductance with potency comparable to that able to depress the activity of th... Channels journals http://www.medworm.com/rss/comments.php?id=2745782 Sun, 30 Aug 2009 20:38:13 +0100 2745782 http://www.medworm.com/index.php?rid=2745781&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19713750%26dopt%3DAbstract Authors: Islas LD, Salazar H, Jara-Oseguera A, Nieto-Posadas A, Llorente I, Rangel-Yescas G, Rosenbaum T The era of molecular structure of ion channels has revealed that their transmembrane segments are alpha helices, as was suspected from hydropathy analysis and experimental data. TRP channels are recent additions to the known families of ion channels, and little structural data is available. In a recent work, we explored the conformational changes occurring at the putative S6 segment of TRPV1 channels; and we observed a periodicity of chemical modification of residues suggestive of an alpha helical structure. Further analysis of the periodicity of the disposition of hydrophobic residues in the S6 segment, suggests that the general architecture of the TRPV1 S6 segment, is very similar... Channels journals http://www.medworm.com/rss/comments.php?id=2745781 Sun, 30 Aug 2009 20:38:11 +0100 2745781 http://www.medworm.com/index.php?rid=2745780&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19713752%26dopt%3DAbstract Authors: Koag MC, Papazian DM The nature and magnitude of voltage sensor conformational changes during ion channel activation are controversial. We have analyzed the topology of the K(V)AP voltage sensor domain in the absence and presence of a hyperpolarized voltage using native, right-side out membrane vesicles from E. coli. This approach does not disrupt the normal membrane environment of the channel protein and does not involve detergent solubilization. We found that voltage-dependent conformational changes are focused in the N-terminal half of the K(V)AP S4 segment, in excellent agreement with results obtained with Shaker. Homologous residues in the K(V)AP and Shaker S4 segments are transferred from the extracellular to the intracellular compartment upon hyperpolarization. Taken to... Channels journals http://www.medworm.com/rss/comments.php?id=2745780 Sun, 30 Aug 2009 20:38:09 +0100 2745780 http://www.medworm.com/index.php?rid=2745779&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19713757%26dopt%3DAbstract Authors: Peters CJ, Vaid M, Horne AJ, Fedida D, Accili EA Cytosolic K(V)beta1 subunits co-assemble with transmembrane K(V)1 channel alpha-subunits and have complex effects on channel function. Fast inactivation, the most obvious effect conferred, is due to fast open channel block resulting from the binding of the N-terminus within the inner mouth of the pore. K(V)beta1 subunits also slow current deactivation, enhance slow inactivation and shift channel activation to more negative voltages, but the mechanisms underlying these actions are not known. Here we use voltage clamp fluorimetry at sites near the extracellular end of the S4 helix, the channel's primary voltage sensor, in combination with voltage clamp electrophysiology, to independently track the movement of the S4 helix along wi... Channels journals http://www.medworm.com/rss/comments.php?id=2745779 Sun, 30 Aug 2009 20:38:07 +0100 2745779 http://www.medworm.com/index.php?rid=2745778&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19713767%26dopt%3DAbstract Authors: Thomsen MB, Foster E, Nguyen KH, Sosunov EA Potassium channel interacting proteins (KChIP) are Ca(2+)-binding proteins that originally were identified as auxiliary subunits for K(V)4 channels. K(V)4 channels encode the voltage gated A-current (I(A)) in neuronal tissue and the fast, transient outward current (I(to,f)) in cardiac tissue. Recently, we have reported that KChIP2 functionally modulates the cardiac Ca(V)1.2-governed L-type Ca(2+) current (I(Ca,L)) through a direct interaction between KChIP2 and the amino-terminus of Ca(V)1.2. Here, we show that KChIP2 and Ca(V)1.2 co-immunoprecipitate enhancing the biochemical support for our previous finding. Using gene-chip and real-time PCR techniques, we find that KChIP2(-/-) mice have an increased transcriptional activity of the... Channels journals http://www.medworm.com/rss/comments.php?id=2745778 Sun, 30 Aug 2009 20:38:05 +0100 2745778 http://www.medworm.com/index.php?rid=2720294&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19690453%26dopt%3DAbstract Authors: Braun AP PMID: 19690453 [PubMed - as supplied by publisher] (Source: Channels) Channels journals http://www.medworm.com/rss/comments.php?id=2720294 Sun, 26 Jul 2009 23:00:00 +0100 2720294 http://www.medworm.com/index.php?rid=2720293&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19690465%26dopt%3DAbstract Authors: Al-Mubarak B, Soriano FX, Hardingham GE Activation of gene expression by FOXO transcription factors can promote neuronal death in response to loss of trophic support, or oxidative stress. The predominant neuronal FOXOs, FOXO1 and FOXO3, promote the expression of pro-death genes, such as Fas Ligand, Bim and Txnip. Neuroprotective signals initiated by neurotrophins, growth factors or synaptic activity trigger the nuclear export of FOXOs via activation of the PI3K-Akt pathway. One key aspect of FOXO regulation is that once PI3K-Akt activity has returned to baseline, FOXOs return to the nucleus to resume the activation of their target genes. Thus, the FOXO-inhibiting capacity of the PI3K-Akt pathway is thought to be short-lived. However, we show here that synaptic NMDA receptor ac... Channels journals http://www.medworm.com/rss/comments.php?id=2720293 Thu, 23 Jul 2009 23:00:00 +0100 2720293 http://www.medworm.com/index.php?rid=2640094&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19625771%26dopt%3DAbstract Authors: Bannister RA, Beam KG Depolarization-induced entry of divalent ions into skeletal muscle has been attributed to a process termed Excitation-Coupled Ca(2+) Entry (ECCE), which is hypothesized to require the interaction of the ryanodine receptor (RyR1), the L-type Ca(2+) channel (DHPR) and another unidentified cation channel. Thus, ECCE is absent in myotubes lacking either the DHPR (dysgenic) or RyR1 (dyspedic). Furthermore, ECCE, as measured by Mn(2+) quench of Fura-2, is reconstituted by expression of a mutant DHPR alpha(1S) subunit (SkEIIIK) thought to be impermeable to divalent cations. Previously, we showed that the bulk of depolarization-induced Ca(2+) entry could be explained by the skeletal L-type current. Accordingly, one would predict that any Ca(2+) current similar to... Channels journals http://www.medworm.com/rss/comments.php?id=2640094 Thu, 23 Jul 2009 23:00:00 +0100 2640094 http://www.medworm.com/index.php?rid=2627297&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19617704%26dopt%3DAbstract In this study, we examined the comparative mechanisms of the channel activation by Ca(2+) and H(+). Steady-state macroscopic conductance-voltage measurements as well as single-channel openings at negative voltages where voltage-sensor activation is negligible showed that at respective saturating concentrations Ca(2+) is more effective in relative stabilization of the open conformation than H(+). Calculations using the Debye-Hückel formalism suggest that small structural changes in the RCK1 sensor, on the order of few angstroms, may accompany the H(+)-mediated opening of the channel. While the efficacy of H(+) in activation of the channel is less than that of Ca(2+), H(+) more effectively accelerates the activation kinetics when examined at the concentrations equipotent on macroscopic ... Channels journals http://www.medworm.com/rss/comments.php?id=2627297 Thu, 16 Jul 2009 23:00:00 +0100 2627297 http://www.medworm.com/index.php?rid=2627296&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19617705%26dopt%3DAbstract In this study, HERG block by quinidine and cisapride was assessed in extracellular solutions of calcium, potassium, rubidium, cesium and tetraethylammonium (TEA) using two-electrode voltage clamping of Xenopus oocytes. Consistent with previous reports we show that increases in extracellular potassium reduce HERG block by quinidine and cisapride. We also show that increasing extracellular rubidium and cesium reduced HERG block by quinidine and cisapride whereas increasing extracellular calcium and extracellular TEA did not alter HERG block by quinidine and cisapride. These results demonstrate that at lower extracellular potassium concentrations, the permeant ion is almost exclusively responsible for the reduction in quinidine and cisapride block of HERG due to increases in extracellular pot... Channels journals http://www.medworm.com/rss/comments.php?id=2627296 Tue, 14 Jul 2009 23:00:00 +0100 2627296 http://www.medworm.com/index.php?rid=2627295&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19617715%26dopt%3DAbstract Authors: Weiss N PMID: 19617715 [PubMed - as supplied by publisher] (Source: Channels) Channels journals http://www.medworm.com/rss/comments.php?id=2627295 Tue, 14 Jul 2009 23:00:00 +0100 2627295 http://www.medworm.com/index.php?rid=2573188&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19574740%26dopt%3DAbstract Authors: Yuan JP, Kim MS, Zeng W, Shin DM, Huang G, Worley PF, Muallem S Store-operated Ca(2+) channels (SOCs) are Ca(2+) influx channels at the plasma membrane whose opening is determined by the level of Ca(2+) stored in the endoplasmic reticulum lumen. SOCs are activated in response to receptor-mediated or passive depletion of ER Ca(2+) to regulate many Ca(2+)-dependent cellular functions. Early work implicated the TRPC channels as SOCs. More recently, it was found that the Orai channels mediate the CRAC current and that the Ca(2+) binding protein STIM1 functions as the ER Ca(2+) sensor that mediates activation of the SOCs in response to depletion of ER Ca(2+). Key questions are whether both TRPC and Orai channels are opened by STIM1 and the molecular mechanism by which STIM1 opens t... Channels journals http://www.medworm.com/rss/comments.php?id=2573188 Mon, 06 Jul 2009 13:32:04 +0100 2573188 http://www.medworm.com/index.php?rid=2547896&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19535914%26dopt%3DAbstract Authors: Tadayonnejad R, Mehaffey WH, Anderson D, Turner RW Deep cerebellar nuclear (DCN) neurons exhibit distinct phenotypes of rebound discharge following current-evoked membrane hyperpolarizations that arise from specific Ca(V)3 T-type Ca(2+) channel isoforms and Ca(2+)-activated K(+) channels. The probability of evoking rebound bursts following a brief train of GABAergic inhibitory synaptic input from cerebellar Purkinje cells was recently questioned for stimulus intensities adjusted to evoke a long post-stimulus pause in spike firing. We revisited this issue to examine the potential for generating rebound bursts in DCN cells in response to synaptic inputs in vitro. Both a Transient and Weak Burst phenotype could be distinguished in on-cell extracellular recordings or whole-cell re... Channels journals http://www.medworm.com/rss/comments.php?id=2547896 Thu, 28 May 2009 23:00:00 +0100 2547896 http://www.medworm.com/index.php?rid=2547894&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19535918%26dopt%3DAbstract Authors: Wang H, Ren D Ion channels can be regulated by a wide spectrum of neurotransmitters and hormones, largely through G-protein-coupled receptors (GPCRs). G-protein-independent activation of ion channel currents by GPCRs has also been recorded, although the molecular identity of the channels and the activation mechanisms remain largely unknown. UNC80 is a protein that is associated with the NALCN Na(+) leak cation channel, and is required for the activation of this channel by the neuropeptide substance P through GPCRs in a G-protein-independent fashion. Here, we show that UNC80 binds Src kinases and recruits Src into the channel complex. This finding is consistent with the known requirement for Src kinases in the activation of NALCN, and may lead to new insights into the molecular... Channels journals http://www.medworm.com/rss/comments.php?id=2547894 Tue, 26 May 2009 23:00:00 +0100 2547894 http://www.medworm.com/index.php?rid=2547898&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19535910%26dopt%3DAbstract Authors: Parnas M, Peters M, Minke B Open channel block (OCB) is a process by which ions bind to the inside of a channel pore and block the flow of ions through that channel. Repulsion of the blocking ions by membrane depolarization is a known mechanism for open channel block removal. For the N-methyl-D-aspartate (NMDA) channel, this mechanism is necessary for channel activation and is involved in neuronal plasticity. Several types of Transient Receptor Potential (TRP) channels, including the Drosophila TRP and TRP-Like (TRPL) channels, also exhibit open channel block. For the Drosophila TRP and TRPL channels, removal of open channel block is necessary for the production of the physiological response to light. Recently, we have shown that lipids such as polyunsaturated fatty acids (PUF... Channels journals http://www.medworm.com/rss/comments.php?id=2547898 Mon, 25 May 2009 23:00:00 +0100 2547898 http://www.medworm.com/index.php?rid=2547906&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19411839%26dopt%3DAbstract Authors: Xu X, Gordon E, Lin Z, Lozinskaya IM, Chen Y, Thorneloe KS Previously we have shown that the transient receptor potential vanilloid 4 (TRPV4) channel regulates urinary bladder function, and that TRPV4 is expressed in both smooth muscle and urothelial cell types within the bladder wall.(1) Urothelial cells have also been suggested to express TRPV1 channels.(2) Therefore, we enzymatically isolated guinea-pig urothelial cells in an attempt to record TRPV4 and TRPV1-mediated currents. The identity of the isolated cells was confirmed by quantitative PCR for the urothelial marker uroplakin 1A. Whole-cell patch-clamp recordings with the TRPV4 agonist, GSK1016790A, activated urothelial currents with an EC(50) of 11 nM that were completely inhibited by the TRPV4 inhibitor ruthenium red... Channels journals http://www.medworm.com/rss/comments.php?id=2547906 Sat, 23 May 2009 23:00:00 +0100 2547906 http://www.medworm.com/index.php?rid=2547902&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19535906%26dopt%3DAbstract In this study, chimeras generated between Na(V)1.2 and Na(V)1.6 were used to test channel domains for sequence that would allow Na(V)1.2 to localize to unmyelinated axons when Na(V)1.6 could not. We show that the N-terminal 202 amino acids of the Na(V)1.2 channel can mediate membrane domain-specific sorting in polarized epithelial cells and are necessary but not sufficient for localizing the isoform to the axons of cultured neurons. The domain-sorting signal is in the region between amino acids 110-202 of the Na(V)1.2 channel. The C-terminal 451 amino acids of Na(V)1.2 likely contain determinants that interact with neuron-specific factors to direct Na(V)1.2 to the axon. PMID: 19535906 [PubMed - as supplied by publisher] (Source: Channels) Channels journals http://www.medworm.com/rss/comments.php?id=2547902 Sat, 23 May 2009 23:00:00 +0100 2547902 http://www.medworm.com/index.php?rid=2547904&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19535897%26dopt%3DAbstract Authors: Bannister RA, Ohrtman JD PMID: 19535897 [PubMed - as supplied by publisher] (Source: Channels) Channels journals http://www.medworm.com/rss/comments.php?id=2547904 Wed, 20 May 2009 23:00:00 +0100 2547904 http://www.medworm.com/index.php?rid=2547890&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19556862%26dopt%3DAbstract Authors: Braun AP PMID: 19556862 [PubMed - as supplied by publisher] (Source: Channels) Channels journals http://www.medworm.com/rss/comments.php?id=2547890 Mon, 11 May 2009 23:00:00 +0100 2547890 http://www.medworm.com/index.php?rid=2547900&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19535907%26dopt%3DAbstract Authors: Misler S, Zhou Z, Dickey AS, Silva AM, Pressel DM, Barnett DW Biphasic insulin secretion in response to glucose, consisting of a transient first phase followed by a progressive second phase, is well described in pancreatic islets. Using single canine beta-cells we have compared the time courses of electrical activity and insulin granule exocytosis to biphasic insulin secretion. Short trains of action potentials, similar those found during first phase insulin secretion, trigger phasic exocytosis from a small pool of insulin granules, likely an immediately releasable pool docked near voltage activated Ca(2+) channels. In contrast, plateau depolarizations to between -35 and -20 mV resembling those during second phase insulin secretion, trigger tonic exocytosis from a larger pool ... Channels journals http://www.medworm.com/rss/comments.php?id=2547900 Sun, 10 May 2009 23:00:00 +0100 2547900 http://www.medworm.com/index.php?rid=2547892&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19556861%26dopt%3DAbstract Authors: Braun AP PMID: 19556861 [PubMed - as supplied by publisher] (Source: Channels) Channels journals http://www.medworm.com/rss/comments.php?id=2547892 Sun, 10 May 2009 23:00:00 +0100 2547892 http://www.medworm.com/index.php?rid=2224505&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19242091%26dopt%3DAbstract Authors: Adams PJ, Garcia E, David LS, Mulatz KJ, Spacey SD, Snutch TP Alternative splicing is known to generate multiple functionally distinct calcium channel variants that exhibit unique spatial and temporal expression patterns. In humans, naturally occurring mutations in genes encoding calcium channel pore forming alpha(1)-subunits are associated with several severe hereditary disorders although it remains to be described whether there exists any relationship between the physiological effects of these mutations and calcium channel splice variation. In the present study, we systematically compare the biophysical effects of three type-1 familial hemiplegic migraine (FHM-1) mutations in two predominant splice variants of the neuronal Ca(V)2.1 P/Q-type channel. All three FHM-1 mutations... Channels journals http://www.medworm.com/rss/comments.php?id=2224505 Sun, 01 Mar 2009 11:37:19 +0100 2224505 http://www.medworm.com/index.php?rid=2224504&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19242115%26dopt%3DAbstract Authors: Misler S, Silva AM, Barnett D, Dickey AS In response to depolarizations that open voltage dependent Ca(2+) channels single porcine beta-cells display heterogeneous time courses of exocytosis. Some cells display phasic exocytosis that is triggered by individual or short burst of action potentials typically characteristic of glucose-induced electrical activity or brief voltage clamp depolarization. Other cells, singularly or additionally, display tonic exocytosis that (i) is triggered during prolonged (up to seconds-long) depolarizations to voltages (-30 to -20 mV), and (ii) coincides with rises in global cytosolic [Ca(2+)] >500 nM. We suggest that tonic exocytosis (i) likely results from a recently described pool of granules that is more Ca2+ sensitive and less co-localized ... Channels journals http://www.medworm.com/rss/comments.php?id=2224504 Sun, 01 Mar 2009 11:37:09 +0100 2224504 http://www.medworm.com/index.php?rid=2224503&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19242122%26dopt%3DAbstract Authors: Silva AM, Dickey AS, Barnett DW, Misler S Given the growing interest in porcine islets as model tissue for studying the pathogenesis of human diabetes mellitus and its treatment by transplantation, we investigated stimulus-exocytosis coupling in single porcine beta-cells using patch clamp electrophysiology, Ca(2+) imaging, capacitance tracking and amperometry. We establish that porcine beta-cells display several features prominently seen in beta-cells from human islets of Langerhans. These include: (i) wide heterogeneity of electrical responsiveness to glucose; (ii) dependence of action potential activity on voltage-dependent Na(+) as well as high voltage activated Ca(2+) current; (iii) heterogeneity of time course of depolarization-evoked insulin granule exocytosis; and (iv) ... Channels journals http://www.medworm.com/rss/comments.php?id=2224503 Sun, 01 Mar 2009 11:37:04 +0100 2224503 http://www.medworm.com/index.php?rid=2196282&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19221510%26dopt%3DAbstract Authors: Zhang MM, McArthur JR, Azam L, Bulaj G, Olivera BM, French RJ, Yoshikami D Tetrodotoxin (TTX) is the quintessential ligand of voltage-gated sodium channels (Na(V)s). Like TTX, mu-conotoxin peptides are pore blockers, and both toxins have helped to define the properties of neurotoxin receptor Site 1 of Na(V)s. Here, we report unexpected results showing that the recently discovered mu-conotoxin KIIIA and TTX can simultaneously bind to Site 1 and act in concert. Results with saturating concentrations of peptide applied to voltage-clamped Xenopus oocytes expressing brain Na(V)1.2, and single-channel recordings from brain channels in lipid bilayers, show that KIIIA or its analog, KIIIA[K7A], block partially, with a residual current that can be completely blocked by TTX. In addition... Channels journals http://www.medworm.com/rss/comments.php?id=2196282 Sun, 25 Jan 2009 05:00:00 +0100 2196282 http://www.medworm.com/index.php?rid=2066274&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19106618%26dopt%3DAbstract Authors: Ravindran A, Kobrinsky E, Lao QZ, Soldatov NM Voltage-activated Ca(V)1.2 calcium channels require association of the pore-forming alpha(1C) subunit with accessory Ca(V)beta and alpha(2)delta subunits. Binding of a single calmodulin (CaM) to alpha(1C) supports Ca(2+)-dependent inactivation (CDI). The human Ca(V)1.2 channel is silent in the absence of Ca(V)beta and/or alpha(2)delta. Recently, we found that coexpression of exogenous CaM (CaM(ex)) supports plasma membrane targeting, gating facilitation and CDI of the channel in the absence of Ca(V)beta. Here we discovered that CaM(ex) and its Ca(2+)-insensitive mutant (CaM(1234)) rendered active alpha(1C)/Ca(V)beta channel in the absence of alpha(2)beta. Coexpression of CaM(ex) with alpha(1C) and beta(2d) in calcium-channel-free C... Channels journals http://www.medworm.com/rss/comments.php?id=2066274 Fri, 26 Dec 2008 17:29:37 +0100 2066274 http://www.medworm.com/index.php?rid=2042836&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19077539%26dopt%3DAbstract Authors: Kurokawa J, Bankston JR, Kaihara A, Chen L, Furukawa T, Kass RS Co-assembly of KCNQ1 with different accessory, or beta, subunits that are members of the KCNE family results in potassium (K(+)) channels that conduct functionally distinct currents. The alpha subunit KCNQ1 conducts a slowly activated delayed rectifier K(+) current (I(Ks)), a major contributor to cardiac repolarization, when co-assembled with KCNE1 and channels that favor the open state when co-assembled with either KCNE2 or KCNE3. In the heart, stimulation of the sympathetic nervous system enhances I(Ks). A macromolecular signaling complex of the I(Ks) channel including the targeting protein Yotiao coordinates up or downregulation of channel activity by protein kinase A (PKA) phosphorylation and dephosphorylation... Channels journals http://www.medworm.com/rss/comments.php?id=2042836 Wed, 17 Dec 2008 21:39:07 +0100 2042836 http://www.medworm.com/index.php?rid=2042835&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19077547%26dopt%3DAbstract Authors: Vaid M, Horne A, Claydon T, Fedida D Fluorescence-based approaches provide powerful techniques to directly report structural dynamics underlying gating processes in Shaker K(V) channels. Here, following on from work carried out in Shaker channels, we have used voltage clamp fluorimetry for the first time to study voltage sensor motions in mammalian K(V)1.5 channels, by attaching TMRM fluorescent probes to substituted cysteine residues in the S3-S4 linker of K(V)1.5 (A397C). Compared with the Shaker channel, there are significant differences in the fluorescence signals that occur on activation of the channel. In addition to a well-understood fluorescence quenching signal associated with S4 movement, we have recorded a unique partial recovery of fluorescence after the quenching ... Channels journals http://www.medworm.com/rss/comments.php?id=2042835 Wed, 17 Dec 2008 21:38:53 +0100 2042835 http://www.medworm.com/index.php?rid=1803884&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18797191%26dopt%3DAbstract In this study we have used a genetic complementation assay of K(+)-auxotrophic E. coli (TK2420) and S. cerevisiae (SGY1528) to identify activatory or 'gain-of-function' mutations which allow functional activity of KcsA in the physiological environment of two markedly different expression systems. These mutations clustered at the helix-bundle-crossing in both TM1 and TM2 (residues H25, L105, A108, T112, W113, F114, E118 and Q119), and include residues previously implicated in the pH-gating mechanism. We discuss how these gain-of-function mutations may result in their activatory phenotype, the relative merits of the E. coli and S. cerevisiae genetic complementation approaches for the identification of gating mutations in prokaryotic K(+) channels, and ways in which this assay may be improved... Channels journals http://www.medworm.com/rss/comments.php?id=1803884 Thu, 18 Sep 2008 19:06:59 +0100 1803884 http://www.medworm.com/index.php?rid=1803883&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18797193%26dopt%3DAbstract Authors: Watschinger K, Horak SB, Schulze K, Obermair GJ, Wild C, Koschak A, Sinnegger-Brauns MJ, Tampé R, Striessnig J Depolarisation-induced Ca(2+) influx into electrically excitable cells is determined by the density of voltage-gated Ca(2+) channels at the cell surface. Surface expression is modulated by physiological stimuli as well as by drugs and can be altered under pathological conditions. Extracellular epitope-tagging of channel subunits allows to quantify their surface expression and to distinguish surface channels from those in intracellular compartments. Here we report the first systematic characterisation of extracellularly epitope-tagged Ca(V)2.1 channels. We identified a permissive region in the pore-loop of repeat IV within the Ca(V)2.1 alpha(1) subunit, which allo... Channels journals http://www.medworm.com/rss/comments.php?id=1803883 Thu, 18 Sep 2008 19:06:54 +0100 1803883 http://www.medworm.com/index.php?rid=1757228&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18728399%26dopt%3DAbstract Authors: Serulle Y, Arancio O, Ziff EB Regulated trafficking of AMPA receptors (AMPARs) is an important mechanism that underlies the activity-dependent modification of synaptic strength. Trafficking of AMPARs is regulated by specific interactions of their subunits with other proteins. Recently, we have reported that the AMPAR subunit GluR1 binds the cGMP-dependent kinase type II (cGKII) adjacent to the kinase catalytic site, and that this interaction is increased by cGMP. In this complex, cGKII phosphorylates GluR1 at serine 845 (S845), a site known to be phosphorylated also by PKA. S845 phosphorylation leads to an increase of GluR1 on the plasma membrane. In neurons, cGMP is produced by soluble guanylate cyclase (sGC), which is activated by nitric oxide (NO). Calcium flux through the ... Channels journals http://www.medworm.com/rss/comments.php?id=1757228 Mon, 04 Aug 2008 04:00:00 +0100 1757228 http://www.medworm.com/index.php?rid=1757231&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18719395%26dopt%3DAbstract We examined the effects of neutralizing each of four negatively charged amino acid residues, Glu-1047, Glu-1052, Asp-1054 and Asp-1059, within the putative pore-forming region of human TRPM7. Mutating Glu-1047 to alanine (E1047A) resulted in non-functional channels, whereas mutating any of the other residues resulted in functionally expressed channels. Cs(+) currents through D1054A and E1052A were less sensitive to block by divalent cations; the IC(50) values were increased 5.5- and 3.9-fold, respectively, for Mg(2+) and 10.5- and 6.7-fold, respectively, for Ca(2+). D1059A also had a significant reduction, though less marked compared to the reductions seen for D1054A and E1052A, in sensitivity to Mg(2+) (1.7-fold) and Ca(2+) (3.9-fold). The D1054A mutation largely abolished inward currents... Channels journals http://www.medworm.com/rss/comments.php?id=1757231 Wed, 30 Jul 2008 04:00:00 +0100 1757231 http://www.medworm.com/index.php?rid=1757229&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18719397%26dopt%3DAbstract Authors: Striessnig J, Koschak A PMID: 18719397 [PubMed - as supplied by publisher] (Source: Channels) Channels journals http://www.medworm.com/rss/comments.php?id=1757229 Fri, 11 Jul 2008 04:00:00 +0100 1757229 http://www.medworm.com/index.php?rid=1757232&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18719394%26dopt%3DAbstract Authors: Kisilevsky AE, Zamponi GW N-type channels are located on dendrites and at pre-synaptic nerve terminals where they play a fundamental role in neurotransmitter release. They are potently regulated by the activation of a number of different types of pertussis toxin (PTX)-sensitive Galpha(i/o) coupled receptors, which results in voltage-dependent inhibition of channel activity via Gbetagamma subunits. Using heterologous expression in HEK 293T cells, we show via whole cell patch clamp recordings that D2 receptors mediate both Gbetagamma (i.e., voltage-dependent) and voltage-independent inhibition of channel activity. Furthermore, using co-immunoprecipitation and pull down assays involving the intracellular regions of each protein, we show that D2 receptors and N-type channels form ... Channels journals http://www.medworm.com/rss/comments.php?id=1757232 Wed, 09 Jul 2008 04:00:00 +0100 1757232 http://www.medworm.com/index.php?rid=1757230&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18719396%26dopt%3DAbstract Authors: Soom M, Gessner G, Heuer H, Hoshi T, Heinemann SH Large-conductance Ca(2+)- and voltage-activated K(+) (BK) channels are comprised of four pore-forming alpha-subunits (Slo1), whose mRNA is alternatively spliced in a cell-specific manner. Here we report the first case of a correctly spliced mutually exclusive exon in a mammalian (human and mouse) BK channel; an exon coding for the region from S6 to the RCK1 domain is exchanged for an alternative exon of the same length. The slo1 transcript with this novel exon is present in native brain tissues and inclusion of the alternative exon profoundly alters the channel's gating characteristics: faster activation at low Ca(2+) concentrations and greater open probability at resting membrane potential at high Ca(2+) concentrations. The no... Channels journals http://www.medworm.com/rss/comments.php?id=1757230 Tue, 08 Jul 2008 04:00:00 +0100 1757230 http://www.medworm.com/index.php?rid=1757255&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690049%26dopt%3DAbstract Authors: Vandenberg RJ, Huang S, Ryan RM Glutamate transporters are unusual proteins in that they can function as both a transporter and a chloride channel. With the recent determination of the crystal structure of an archaeal aspartate transporter it is now possible to begin to put together a physical picture of how these proteins are able to carry out their dual functions. In this review we shall discuss our current understanding of the functional states of glutamate transporters and how they may arise. We will also discuss some of the alternate conducting states of glutamate transporters and provide definitions of the various states. PMID: 18690049 [PubMed - in process] (Source: Channels) Channels journals http://www.medworm.com/rss/comments.php?id=1757255 Tue, 01 Jan 2008 05:00:00 +0100 1757255 http://www.medworm.com/index.php?rid=1757254&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690050%26dopt%3DAbstract Authors: Poburko D, Fameli N, Kuo KH, van Breemen C Following the recent observation of localized cytosolic subplasmalemmal [Na+] elevations (LNats) in rat aortic smooth muscle cells, we discuss here the current evidence for the structural and molecular roles of cytosolic nanodomains at close junctions of the plasma membrane (PM) and sarcoplasmic reticulum (SR) in the generation of LNats. These junctions, the loss of which might contribute to vascular aging and disease, provide a platform for ion metabolism signalplexes and the interaction of localized Na+ and Ca2+ gradients. We moreover suggest the existence in the junctions of a Na+ diffusional barrier as a necessary condition for the generation of LNats. LNats are likely a fundamental feature of near membrane ion signaling in many c... Channels journals http://www.medworm.com/rss/comments.php?id=1757254 Tue, 01 Jan 2008 05:00:00 +0100 1757254 http://www.medworm.com/index.php?rid=1757253&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690051%26dopt%3DAbstract Authors: Jin T, Sui JL, Rosenhouse-Dantsker A, Chan KW, Jan LY, Logothetis DE Phosphatidylinositol bisphosphate (PIP(2)) is the most abundant phosphoinositide in the plasma membrane of cells and its interaction with many ion channel proteins has proven to be a critical factor enabling ion channel gating. All members of the inwardly rectifying potassium (Kir) channel family depend on PIP(2) for their activity, displaying distinct affinities and stereospecificities of interaction with the phosphoinositide. Here, we explored the stoichiometry of Kir channels with PIP(2). We first showed that PIP(2) regulated the activity of Kir3.4 channels mainly by altering their bursting behavior. Detailed burst analysis indicates that the channels assumed up to four open states and a connectivity of fo... Channels journals http://www.medworm.com/rss/comments.php?id=1757253 Tue, 01 Jan 2008 05:00:00 +0100 1757253 http://www.medworm.com/index.php?rid=1757252&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690052%26dopt%3DAbstract Authors: Heblich F, Tran Van Minh A, Hendrich J, Watschinger K, Dolphin AC The mechanism of action of gabapentin is still not well understood. It binds to the alpha(2)delta-1 and alpha(2)delta-2 subunits of voltage-gated calcium channels but has little acute effect on calcium currents in several systems. However, our recent results conclusively demonstrated that gabapentin inhibited calcium currents when applied chronically but not acutely, both in heterologous expression systems and in dorsal root ganglion neurons.(1) In that study we only examined a 40-hour time point of incubation with gabapentin, and here we have extended these results to include the effect of up to 6 and 20 hours incubation with gabapentin on calcium channel currents formed from Ca(V)2.1/beta(4)/alpha(2)delta-2 su... Channels journals http://www.medworm.com/rss/comments.php?id=1757252 Tue, 01 Jan 2008 05:00:00 +0100 1757252 http://www.medworm.com/index.php?rid=1757251&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690053%26dopt%3DAbstract Authors: Grudzinska J, Schumann T, Schemm R, Betz H, Laube B The divalent cation Zn2+ has been shown to regulate inhibitory neurotransmission in the mammalian CNS by affecting the activation of the strychnine-sensitive glycine receptor (GlyR). In spinal neurons and cells expressing recombinant GlyRs, low micromolar (<10 microM) concentrations of Zn2+ enhance glycine currents, whereas higher concentrations (>10 microM) have an inhibitory effect. Mutational studies have localized the Zn2+ binding sites mediating allosteric potentiation and inhibition of GlyRs in distinct regions of the N-terminal extracellular domain of the GlyR alpha-subunits. Here, we examined the Zn2+ sensitivity of different mutations within the agonist binding site of the homomeric alpha(1)-subunit GlyR upon h... Channels journals http://www.medworm.com/rss/comments.php?id=1757251 Tue, 01 Jan 2008 05:00:00 +0100 1757251 http://www.medworm.com/index.php?rid=1757250&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690054%26dopt%3DAbstract Authors: Groome JR, Larsen MF, Coonts A We investigated effects of paramyotonia congenita mutations F1473S and F1705I on gating of skeletal muscle Na+ channels. We used on-cell recordings from Xenopus oocytes to compare fast inactivation and deactivation in wild-type and mutant channels. Then, we used gating current recordings to determine how these actions of PC mutants might be reflected in their effects on charge movement and its immobilization. F1473S, but not F1705I, accelerated deactivation from the inactivated state and enhanced the remobilization of gating charge. F1473S and F1705I decreased the completion of closed-state fast inactivation, and decreased charge movement over the voltage range at which channels did not activate. An unexpected result was that F1705I increased the... Channels journals http://www.medworm.com/rss/comments.php?id=1757250 Tue, 01 Jan 2008 05:00:00 +0100 1757250 http://www.medworm.com/index.php?rid=1757249&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690055%26dopt%3DAbstract Authors: Cheng WW, Tong A, Flagg TP, Nichols CG Sulfonylurea receptors (SURs) associate with Kir6.x subunits to form tetradimeric K(ATP) channel complexes. SUR1 and SUR2 confer differential channel sensitivities to nucleotides and pharmacological agents, and are expressed in specific, but overlapping, tissues. This raises the question of whether these different SUR subtypes can assemble in the same channel complex and generate channels with hybrid properties. To test this, we engineered dimeric constructs of wild type or N160D mutant Kir6.2 fused to SUR1 or SUR2A. Dimeric fusions formed functional, ATP-sensitive, channels. Coexpression of weakly rectifying SUR1-Kir6.2 (WTF-1) with strongly rectifying SUR1-Kir6.2[N160D] (NDF-1) in COSm6 cells results in mixed subunit complexes that exhi... Channels journals http://www.medworm.com/rss/comments.php?id=1757249 Tue, 01 Jan 2008 05:00:00 +0100 1757249 http://www.medworm.com/index.php?rid=1757248&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690056%26dopt%3DAbstract Authors: Ahern CA, Eastwood AL, Dougherty DA, Horn R Antiarrhythmics, anticonvulsants and local anesthetics inhibit voltage-gated sodium channels and reduce membrane excitability in neurons and muscle, making them useful in the management of cardiac arrhythmias, epilepsy and pain. These compounds, which are often termed singly in the literature as 'local anesthetics', have at least two inhibitory states: a resting inhibition that develops with intermittent stimulation and a higher affinity inhibition that arises upon repeated depolarization and likely involves the inactivated state of the channel. Although elucidating their mechanism of inhibition has been an active area of research for decades, many questions remain unanswered. Do these two inhibitory states share a common, but guarde... Channels journals http://www.medworm.com/rss/comments.php?id=1757248 Tue, 01 Jan 2008 05:00:00 +0100 1757248 http://www.medworm.com/index.php?rid=1757261&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690043%26dopt%3DAbstract We reported that the introduction of delta2 amino acids in the domain preceding the first transmembrane domain in GluR1 resulted in a mutant receptor that displayed all characteristics of lurcher-typical gating. We proposed that lurcher-like mutations work to enhance gating by destabilizing the closed state of the receptor. As a result, no or minimal conformational changes in the ligand-binding domain are sufficient for gating, explaining, respectively, why spontaneous currents occur and competitive antagonists act as partial agonists in lurcher-like channels. Strikingly, a similar conversion of antagonists upon coexpression of glutamate receptors with TARPs has recently been reported.(6,7) We take this as indication that the actual mechanism of action might be very similar, and that both ... Channels journals http://www.medworm.com/rss/comments.php?id=1757261 Thu, 01 Nov 2007 04:00:00 +0100 1757261 http://www.medworm.com/index.php?rid=1757260&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690044%26dopt%3DAbstract Authors: Navarro-Tableros V, Fiordelisio T, Hernandez-Cruz A, Hiriart M Neonatal beta cells are functionally immature as they secrete less insulin than adults and lack of glucose response. The mechanisms that participate in the functional maturation of these cells are not known. Adult rat beta cells synthesize and secrete nerve growth factor (NGF) and express NGF receptors. NGF increases glucose-induced insulin secretion by modulating electrical activity in adult beta cells. In this work, we explored if NGF is involved in the maturation of glucose-induced insulin secretion coupling in rat neonate beta-cells. PMID: 18690044 [PubMed - in process] (Source: Channels) Channels journals http://www.medworm.com/rss/comments.php?id=1757260 Thu, 01 Nov 2007 04:00:00 +0100 1757260 http://www.medworm.com/index.php?rid=1757259&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690045%26dopt%3DAbstract Authors: Lin MC, Papazian DM HERG (KCNH2) and ether-à-go-go (eag) (KCNH1) are members of the same subfamily of voltage-gated K+ channels. In eag, voltage-dependent activation is significantly slowed by extracellular divalent cations. To exert this effect, ions bind to a site located between transmembrane segments S2 and S3 in the voltage sensor domain where they interact with acidic residues that are conserved only among members of the eag subfamily. In HERG channels, extracellular divalent ions significantly accelerate deactivation. To investigate the ionbinding site in HERG, acidic residues in S2 and S3 were neutralized singly or in pairs to alanine, and the functional effects of extracellular Mg(2+) were characterized in Xenopus oocytes. To modulate deactivation kinetics in HER... Channels journals http://www.medworm.com/rss/comments.php?id=1757259 Thu, 01 Nov 2007 04:00:00 +0100 1757259 http://www.medworm.com/index.php?rid=1757258&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690046%26dopt%3DAbstract Authors: Kistler T, Fleck MW Differences in binding-site residues of GluR2 (AMPAR) and GluR6 (KAR) subunits have been identified that might account for their functional and pharmacological differences. Specifically, residues A518, A689 and N721 in GluR6 replace highly conserved threonine and serine residues found in other ionotropic glutamate receptor (iGluR) subunits. To define how these natural substitutions impact GluR6 function, we used patch clamp recording with ultrafast perfusion to characterize the effects of A518T, A689S and N721T on agonist potency, efficacy and response kinetics. We find these natural substitutions impact GluR6 function less than would be expected from reverse mutations in other iGluRs. There was little effect of individual or combined mutations on glutamate... Channels journals http://www.medworm.com/rss/comments.php?id=1757258 Thu, 01 Nov 2007 04:00:00 +0100 1757258 http://www.medworm.com/index.php?rid=1757257&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690047%26dopt%3DAbstract Authors: Chaptal V, Besserer GM, Ottolia M, Nicoll DA, Cascio D, Philipson KD, Abramson J Spatial and temporal regulation of intracellular Ca2+ concentrations is a fundamental requirement for life. The mammalian cardiac Na+-Ca2+ exchanger serves as the main mechanism for Ca2+ efflux after heart contraction. Exchange activity is highly regulated by intracellular Ca2+, which binds two regulatory domains (CBD1 and CBD2) and triggers the full activity of the exchanger. We solved the X-ray crystallographic structure of CBD2 in the presence and absence of Ca2+. Together with mutational analysis of the Ca2+ binding sites, this study reveals the crucial role of one of the two bound Ca2+ ions and helps propose hypotheses on the mechanism of regulation of the exchanger. PMID: 18690047 [PubMe... Channels journals http://www.medworm.com/rss/comments.php?id=1757257 Thu, 01 Nov 2007 04:00:00 +0100 1757257 http://www.medworm.com/index.php?rid=1757256&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690048%26dopt%3DAbstract Authors: Beech DJ, Sukumar P The most widely studied stimuli for ion channel activation are changes in membrane voltage and binding of a chemical ligand in a pocket of the channel protein. While modulation by redox potential has also been appreciated our study shows previously unrecognised channel activation via electron donation from the extracellular redox protein thioredoxin (TRX).(1) The ion channel type involved is a member of the Transient Receptor Potential (TRP) family. Activation by TRX led us to consider the relevance of TRP channels to the inflammatory condition of rheumatoid arthritis, where functions of ion channels are relatively unknown and TRX concentrations are high. TRP channel activation was found to be inhibitory for secretion of matrix metalloproteinases, suggestin... Channels journals http://www.medworm.com/rss/comments.php?id=1757256 Thu, 01 Nov 2007 04:00:00 +0100 1757256 http://www.medworm.com/index.php?rid=1757269&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690035%26dopt%3DAbstract Authors: Rapedius M, Paynter JJ, Fowler PW, Shang L, Sansom MS, Tucker SJ, Baukrowitz T Inhibition by intracellular H(+) (pH gating) and activation by phosphoinositides such as PIP(2) (PIP(2)-gating) are key regulatory mechanisms in the physiology of inwardly-rectifying potassium (Kir) channels. Our recent findings suggest that PIP(2) gating and pH gating are controlled by an intra-subunit H-bond at the helix-bundle crossing between a lysine in TM1 and a backbone carbonyl group in TM2. This interaction only occurs in the closed state and channel opening requires this H-bond to be broken, thereby influencing the kinetics of PIP(2) and pH gating in Kir channels. In this addendum, we explore the role of H-bonding in heteromeric Kir4.1/Kir5.1 channels. Kir5.1 subunits do not possess a TM1 ... Channels journals http://www.medworm.com/rss/comments.php?id=1757269 Sat, 01 Sep 2007 04:00:00 +0100 1757269 http://www.medworm.com/index.php?rid=1757268&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690036%26dopt%3DAbstract Authors: Newell EW, Stanley EF, Schlichter LC Phagocytosis and the ensuing NADPH-mediated respiratory burst are important aspects of microglial activation that require calcium ion (Ca(2+)) influx. However, the specific Ca(2+) entry pathway(s) that regulates this mechanism remains unclear, with the best candidates being surface membrane Ca(2+)-permeable ion channels or Na(+)/Ca(2+) exchangers. In order to address this issue, we used quantitative real-time RT-PCR to assess mRNA expression of the Na(+)/Ca(2+) exchangers, Slc8a1-3/NCX1-3, before and after phagocytosis by rat microglia. All three Na(+)/Ca(2+) exchangers were expressed, with mRNA levels of NCX1 > NCX3 > NCX2, and were unaltered during the one hour phagocytosis period. We then carried out a biophysical characterization ... Channels journals http://www.medworm.com/rss/comments.php?id=1757268 Sat, 01 Sep 2007 04:00:00 +0100 1757268 http://www.medworm.com/index.php?rid=1757267&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690037%26dopt%3DAbstract Authors: Nassirpour R, Slesinger PA G protein-gated inwardly rectifying potassium (Kir3) channels are involved in regulating membrane excitability in the brain. Kir3 channels have been shown to play a role in learning, analgesia and drug addiction. Little is known about the cell surface regulation of Kir3 channels. Using a proteomics approach, we recently discovered that sorting nexin 27 (SNX27) associates with a subset of Kir3 channels. Sorting nexins have been implicated in trafficking of proteins through endosomal compartments. The single PDZ domain of SNX27 binds directly to the PDZ binding motif of Kir3 channels leading to their downregulation. Here, we examined the functional effect of SNX27b expression on different subunit combinations of the Kir3 family. Our results show that r... Channels journals http://www.medworm.com/rss/comments.php?id=1757267 Sat, 01 Sep 2007 04:00:00 +0100 1757267 http://www.medworm.com/index.php?rid=1757266&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690038%26dopt%3DAbstract Authors: Marom M, Sebag A, Atlas D Strontium (Sr(2+)), Barium (Ba(2+)) and Lanthanum (La(3+)) can substitute for Ca(2+) in driving synaptic transmission during membrane depolarization. Ion recognition at the polyglutamate motif (EEEE), comprising the channel selectivity-filter, during voltage-driven transitions, controls the kinetics of the voltage-gated calcium channel (VGCC) and its interactions with the synaptic proteins. We tested the effect of different charge carriers on evoked-release, as a means of exploring the involvement of VGCC in the fusion pore configuration. Employing amperometry recordings in single bovine chromaffin cells we show that the size of the fusion pore, designated by the 'foot'-amplitude, was increased when Ba(2+) substituted for Ca(2+) and decreased, with La... Channels journals http://www.medworm.com/rss/comments.php?id=1757266 Sat, 01 Sep 2007 04:00:00 +0100 1757266 http://www.medworm.com/index.php?rid=1757265&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690039%26dopt%3DAbstract Authors: Li J, Marionneau C, Koval O, Zingman L, Mohler PJ, Nerbonne JM, Anderson ME Mice with genetic inhibition (AC3-I) of the multifunctional Ca(2+)/calmodulin dependent protein kinase II (CaMKII) have improved cardiomyocyte survival after ischemia. Some K(+) currents are up-regulated in AC3-I hearts, but it is unknown if CaMKII inhibition increases the ATP sensitive K(+) current (I(KATP)) that underlies ischemic preconditioning (IP) and confers resistance to ischemia. We hypothesized increased I(KATP) was part of the mechanism for improved ventricular myocyte survival during ischemia in AC3-I mice. AC3-I hearts were protected against global ischemia due to enhanced IP compared to wild type (WT) and transgenic control (AC3-C) hearts. IKATP was significantly increased, while the nega... Channels journals http://www.medworm.com/rss/comments.php?id=1757265 Sat, 01 Sep 2007 04:00:00 +0100 1757265 http://www.medworm.com/index.php?rid=1757264&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690040%26dopt%3DAbstract Authors: Kloda A, Martinac B, Adams DJ Glutamate-activated N-methyl-D-aspartate (NMDA) receptors are ligand-gated ion channels, which mediate synaptic transmission, long-term potentiation, synaptic plasticity and neurodegeneration via conditional Ca(2+) signalling. Recent crystallographic studies have focussed on solving the structural determinant of the ligand binding within the core region of NR1 and NR2 subunits. Future structural analysis will help to understand the mechanism of native channel activation and regulation during synaptic transmission. A number of NMDA receptor ligands have been identified which act as positive or negative modulators of receptor function. There is evidence that the lipid bilayer can further regulate the activity of the NMDA receptor channels. Modulator... Channels journals http://www.medworm.com/rss/comments.php?id=1757264 Sat, 01 Sep 2007 04:00:00 +0100 1757264 http://www.medworm.com/index.php?rid=1757263&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690041%26dopt%3DAbstract Authors: Choudhary G, Aliste MP, Tieleman DP, French RJ, Dudley SC mu-Conotoxin GIIIA (mu-CTX) is a high-affinity ligand for the outer vestibule of selected isoforms of the voltage-gated Na(+) channel. The detailed bases for the toxin's high affinity binding and isoform selectivity are unclear. The outer vestibule is lined by four pore-forming (P) loops, each with an acidic residue near the mouth of the vestibule. mu-CTX has seven positively charged residues that may interact with these acidic P-loop residues. Using pair-wise alanine replacement of charged toxin and channel residues, in conjunction with double mutant cycle analysis, we determined coupling energies for specific interactions between each P-loop acidic residue and selected toxin residues to systematically establish quanti... Channels journals http://www.medworm.com/rss/comments.php?id=1757263 Sat, 01 Sep 2007 04:00:00 +0100 1757263 http://www.medworm.com/index.php?rid=1757262&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690042%26dopt%3DAbstract In this study we extend this previous analysis by analyzing NO-activated soluble guanylyl cyclase (sGC) expression in the heart (ferret and human). We demonstrate that, at both tissue and single myocyte levels, sGC protein expression is heterogeneous, being high in sinoatrial node, right atrium, right ventricle and left ventricular subepicardium, but markedly reduced to absent in left atrium and left ventricular subendocardium. Thus, there is a significant overlap in expression gradients of sGC, eNOS, and ECSOD among distinct cardiac tissue and myocyte types. These gradients positively correlate with both: (i) experimentally measured basal NO production levels; and (ii) expression gradients of specific voltage-gated ion channels (particularly Kv1 and Kv4 channels). Our results provide the ... Channels journals http://www.medworm.com/rss/comments.php?id=1757262 Sat, 01 Sep 2007 04:00:00 +0100 1757262 http://www.medworm.com/index.php?rid=1757247&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18698149%26dopt%3DAbstract Authors: Leipold E, DeBie H, Zorn S, Borges A, Olivera BM, Terlau H, Heinemann SH The muO-conotoxins MrVIA and MrVIB are 31-residue peptides from Conus marmoreus, belonging to the O-superfamily of conotoxins with three disulfide bridges. They have attracted attention because they are inhibitors of tetrodotoxin-insensitive voltage-gated sodium channels (Na(V)1.8) and could therefore serve as lead structure for novel analgesics. The aim of this study was to elucidate the molecular mechanism by which muO-conotoxins affect Na(V) channels. Rat Na(V)1.4 channels and mutants thereof were expressed in mammalian cells and were assayed with the whole-cell patch-clamp method. Unlike for the M-superfamily mu-conotoxin GIIIA from Conus geographus, channel block by MrVIA was strongly diminished afte... Channels journals http://www.medworm.com/rss/comments.php?id=1757247 Sun, 01 Jul 2007 04:00:00 +0100 1757247 http://www.medworm.com/index.php?rid=1757246&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18698150%26dopt%3DAbstract Authors: Soldovieri MV, Miceli F, Bellini G, Coppola G, Pascotto A, Taglialatela M Almost ten years have passed since the identification of Kv7.2 and Kv7.3, the genes altered in Benign Familial Neonatal Seizures (BFNS), a familial autosomal dominant focal epilepsy of the newborn. Despite the rarity of the disease, clinical and genetic data have been gathered from more than 50 BFNS-affected families; these studies reveal that each family harbours a specific disease-causing mutation, and that the mutation-induced functional changes range from a subtle alteration in channel behaviour to a complete ablation of channel function. Prompted by the recent identification of peculiar gating changes in Kv7.2 subunits caused by novel mutations responsible for BFNS, in the present work we attempt to... Channels journals http://www.medworm.com/rss/comments.php?id=1757246 Sun, 01 Jul 2007 04:00:00 +0100 1757246 http://www.medworm.com/index.php?rid=1757243&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18708742%26dopt%3DAbstract Authors: Amadi CC, Brust RD, Skerritt MR, Campbell DL Mechanisms underlying Kv4 channel inactivation and recovery are presently unclear, although there is general consensus that the basic characteristics of these processes are not consistent with Shaker (Kv1) N- and P/C-type mechanisms. Kv4 channels also differ from Shaker in that they can undergo significant inactivation from pre-activated closed-states (closed-state inactivation, CSI), and that inactivation and recovery kinetics can be regulated by intracellular KChIP2 isoforms. To gain insight into the mechanisms regulating Kv4.3 CSI and recovery, we have analyzed the effects of increasing [K(+)](o) from 2 mM to 98 mM in the absence and in the presence of KChIP2b, the major KChIP2 isoform expressed in the mammalian ventricle. In the... Channels journals http://www.medworm.com/rss/comments.php?id=1757243 Sun, 01 Jul 2007 04:00:00 +0100 1757243 http://www.medworm.com/index.php?rid=1757242&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18708743%26dopt%3DAbstract Authors: Balijepalli RC, Delisle BP, Balijepalli SY, Foell JD, Slind JK, Kamp TJ, January CT The localization of ion channels to specific membrane microdomains can impact the functional properties of channels and their role in cellular physiology. We determined the membrane localization of human Kv11.1 (hERG1) alpha-subunit protein, which underlies the rapidly activating, delayed rectifier K(+) current (I(Kr)) in the heart. Immunocytochemistry and membrane fractionation using discontinuous sucrose density gradients of adult canine ventricular tissue showed that Kv11.1 channel protein localized to both the cell surface and T-tubular sarcolemma. Furthermore, density gradient membrane fractionation using detergent (Triton X-100) and non-detergent (OptiPrep) methods from canine ventricular... Channels journals http://www.medworm.com/rss/comments.php?id=1757242 Sun, 01 Jul 2007 04:00:00 +0100 1757242 http://www.medworm.com/index.php?rid=1757241&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18708744%26dopt%3DAbstract Authors: Bankston JR, Sampson KJ, Kateriya S, Glaaser IW, Malito DL, Chung WK, Kass RS Inherited mutations of SCN5A, the gene that encodes Na(V)1.5, the alpha subunit of the principle voltage-gated Na(+) channel in the heart, cause congenital Long QT Syndrome variant 3 (LQT-3) by perturbation of channel inactivation. LQT-3 mutations induce small, but aberrant, inward current that prolongs the ventricular action potential and subjects mutation carriers to arrhythmia risk dictated in part by the biophysical consequences of the mutations. Most previously investigated LQT-3 mutations are associated with increased arrhythmia risk during rest or sleep. Here we report a novel LQT-3 mutation discovered in a pediatric proband diagnosed with LQTS but who experienced cardiac events during periods... Channels journals http://www.medworm.com/rss/comments.php?id=1757241 Sun, 01 Jul 2007 04:00:00 +0100 1757241 http://www.medworm.com/index.php?rid=1757240&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18708745%26dopt%3DAbstract In conclusion, polyamines inhibit neuronal VACCs via complex interactions with extracellular H(+) and Ca. Many of the observed effects can be explained by a model incorporating polyamine binding, H(+) binding and surface charge screening. PMID: 18708745 [PubMed - in process] (Source: Channels) Channels journals http://www.medworm.com/rss/comments.php?id=1757240 Sun, 01 Jul 2007 04:00:00 +0100 1757240 http://www.medworm.com/index.php?rid=1757239&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18708746%26dopt%3DAbstract Authors: Dellisanti CD, Yao Y, Stroud JC, Wang ZZ, Chen L Neurotoxins from snake venoms act as potent antagonists on the nicotinic acetylcholine receptors (nAChRs). Alpha-neurotoxins such as alpha-bungarotoxin (alpha-Btx) selectively bind to the skeletal muscle nAChRs among other subtypes, causing failure of the neuromuscular transmission. Through evolution, some species including snakes and mongoose have developed resistance to alpha-neurotoxins via specific amino acid substitutions in their muscle-type nAChR alpha1 subunit, which constitutes most of the toxin-binding site. Here we analyze these sequence variations in the context of our recent crystal structure of the extracellular domain of the mouse nAChR alpha1 bound to alpha-Btx. Our structure suggests that alpha-Btx has evolved a... Channels journals http://www.medworm.com/rss/comments.php?id=1757239 Sun, 01 Jul 2007 04:00:00 +0100 1757239 http://www.medworm.com/index.php?rid=1757238&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18708747%26dopt%3DAbstract Authors: Ijjaali I, Barrere C, Nargeot J, Petitet F, Bourinet E T-type calcium channels are involved in the generation of rhythmical firing patterns in the mammalian central nervous system and in various pathological alterations of neuronal excitability such as in epilepsy or neuropathic pain. In the search for new T-type calcium channel blockers that would help to treat these disorders, we have followed a bi-dimensional pharmacophore-based virtual screening approach to identify new inhibitors. Nineteen molecules extracted from AurSCOPE Ion Channels knowledgebase were used as query molecules to screen an external database. This in silico approach was then validated using electrophysiology. Interestingly, 16 compounds out of 38 distinct molecules tested showed more than 50% blockade of ... Channels journals http://www.medworm.com/rss/comments.php?id=1757238 Sun, 01 Jul 2007 04:00:00 +0100 1757238 http://www.medworm.com/index.php?rid=1757237&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18708748%26dopt%3DAbstract Authors: Ijjaali I, Dubus E, Bourinet E, Petitet F The aim of the present work is to assess the chemical and biological diversity of ligands reported in scientific articles or patents to be active against ion channels targets. A specific query of the AurSCOPE Ion Channel knowledge database was constructed to retrieve a set of the most active non-peptide ligands tested in binding or electrophysiology experiments against all ion channel families. A biological activity threshold cutoff expressed by K(i), IC(50), or EC(50) was set to 300 nM. This activity cutoff was selected such that we would retrieve a set of compounds, which contain the most active ligands for all target families, but is a reasonable number to analyze. To encode the chemical space for the entire active dataset (9897 mol... Channels journals http://www.medworm.com/rss/comments.php?id=1757237 Sun, 01 Jul 2007 04:00:00 +0100 1757237 http://www.medworm.com/index.php?rid=1757236&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18708749%26dopt%3DAbstract Authors: Lipscombe D, Raingo J How many different calcium channels does it take to make a nervous system? The answer: more than any of us predicted. In 1975 Hagiwara and colleagues published the first evidence that functionally different calcium channels are expressed in cells. By 1999, the calcium channel family could boast ten members, each member defined by a unique set of attributes to support their cellular functions and by unique amino acid sequences. Although nine of these genes are expressed in the nervous system, that number still seemed insufficient to support the wide spectrum of neuronal functions controlled by voltage-gated calcium channels. This discrepancy is probably explained by alternative pre-messenger RNA splicing which substantially expands the number of protein ac... Channels journals http://www.medworm.com/rss/comments.php?id=1757236 Sun, 01 Jul 2007 04:00:00 +0100 1757236 http://www.medworm.com/index.php?rid=1757235&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18708750%26dopt%3DAbstract Authors: Masia R, Caputa G, Nichols CG ATP-sensitive K(+) (K(ATP)) channels are oligomeric complexes of pore-forming Kir6 subunits and regulatory Sulfonylurea Receptor (SUR) subunits. SUR, an ATP-Binding Cassette (ABC) transporter, confers Mg-nucleotide stimulation to the channel via nucleotide interactions with its two cytoplasmic domains (Nucleotide Binding Folds 1 and 2; NBF1 and NBF2). Regulation of K(ATP) channel expression is a complex process involving subunit assembly in the ER, SUR glycosylation in the Golgi, and trafficking to the plasma membrane. Dysregulation can occur at different steps of the pathway, as revealed by disease-causing mutations. Here, we have addressed the role of SUR1 NBF1 in gating and expression of reconstituted channels. Deletion of NBF1 severely impairs... Channels journals http://www.medworm.com/rss/comments.php?id=1757235 Sun, 01 Jul 2007 04:00:00 +0100 1757235 http://www.medworm.com/index.php?rid=1757234&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18708751%26dopt%3DAbstract Authors: Todorovic SM, Jevtovic-Todorovic V Recent evidence strongly suggests that both central and peripheral T-type Ca(2+) channels enhance somatic and visceral nociceptive inputs, as well as that regulation of T-type Ca(2+) channel function can result in significant changes of pain threshold in a variety of animal models. Therefore, T-type Ca(2+) channels in peripheral and central pain pathways, although previously unrecognized, may have great importance as targets for developing new therapies against pain. This is particularly critical in cases in which currently available treatments are limited due to serious side effects or are not consistently effective (e.g., chronic neuropathic pain). In this review, we summarize recent studies of the regulation of T-type channels in periphera... Channels journals http://www.medworm.com/rss/comments.php?id=1757234 Sun, 01 Jul 2007 04:00:00 +0100 1757234 http://www.medworm.com/index.php?rid=1757233&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18711860%26dopt%3DAbstract Authors: Zarayskiy V, Monje F, Peter K, Csutora P, Khodorov BI, Bolotina VM Store-operated channels (SOC) are known to be physiologically activated following agonist-induced IP3 production and depletion of Ca2+ stores. Here we present molecular,biophysical and mechanistic evidence that two ubiquitously expressed plasma membrane channels may be responsible for creating a complex and sometimes controversial SOC image: one being a real SOC encoded by Orai1 and activated exclusively upon depletion of Ca2+ stores (via iPLA2beta -dependent pathway), while the second one is an IP3 receptor-operated channel (IP3ROC) encoded by TRPC1 and activated via its conformational coupling with IP3 receptor. In RBL-2H3 cells endogenously expressing Orai1 and TRPC1, we unmasked and characterized whole-cell... Channels journals http://www.medworm.com/rss/comments.php?id=1757233 Sun, 01 Jul 2007 04:00:00 +0100 1757233 http://www.medworm.com/index.php?rid=1757280&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690024%26dopt%3DAbstract In this report we tested a hypothesis that Na(+) ions traverse a narrow gap between bound BTX and residue N927 at D2S6 of cardiac hNa(v)1.5 Na(+) channels. We found that BTX at 5 microM indeed elicited a strong block of hNa(v)1.5-N927K currents (approximately 70%) after 1000 repetitive pulses (+50 mV/20 ms at 2 Hz) without any effects on Na(+) channel gating. Once occurred, this unique use-dependent block of hNa(v)1.5-N927K Na(+) channels recovered little at holding potential (-140 mV), demonstrating that BTX block is irreversible under our experimental conditions. Such an irreversible effect likewise developed in fast inactivation-deficient hNa(v)1.5-N927K Na(+) channels albeit with a faster on-rate; approximately 90% of peak Na(+) currents were abolished by BTX after 200 repetitive pulse... Channels journals http://www.medworm.com/rss/comments.php?id=1757280 Tue, 01 May 2007 04:00:00 +0100 1757280 http://www.medworm.com/index.php?rid=1757279&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690025%26dopt%3DAbstract Authors: Rosenhouse-Dantsker A, Logothetis DE Potassium channel activation regulates cellular excitability, such as in neuronal and cardiac cells. Regulation of ion channel activity relies on a switching mechanism between two major conformations, the open and closed states, known as gating. It has been suggested that potassium channels are generally gated via a pivoted mechanism the pore-lining helix (TM2) in the proximity of a glycine that is conserved in about 80% of potassium channels, even though about 20% of the channels lack a glycine at this position. Yet, as we show in G-protein gated potassium (Kir3) channels that lack a glycine at this position, the betagamma subunits of G-proteins can still stimulate channel activity. Our results suggest that the effect of mutation of the ce... Channels journals http://www.medworm.com/rss/comments.php?id=1757279 Tue, 01 May 2007 04:00:00 +0100 1757279 http://www.medworm.com/index.php?rid=1757278&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690026%26dopt%3DAbstract Authors: Phelps CB, Procko E, Lishko PV, Wang RR, Gaudet R Ion channels are often modulated by intracellular calcium levels. TRPV1, a channel responsible for the burning pain sensation in response to heat, acid or capsaicin, is desensitized at high intracellular calcium concentrations. We recently identified a multiligand-binding site in the N-terminal ankyrin repeat domain (ARD) of TRPV1 that binds ATP and sensitizes the channel. Calcium-calmodulin binds the same site and is necessary for calcium-mediated TRPV1 desensitization. Here, we examine in more detail the conservation of this TRPV1 multiligand-binding site in other species. Furthermore, using sequence analysis, we determine that the unusually twisted shape of the TRPV1-ARD is likely conserved in other TRPV channels, but not in... Channels journals http://www.medworm.com/rss/comments.php?id=1757278 Tue, 01 May 2007 04:00:00 +0100 1757278 http://www.medworm.com/index.php?rid=1757277&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690027%26dopt%3DAbstract Authors: Miki T, Kiyonaka S, Uriu Y, De Waard M, Wakamori M, Beedle AM, Campbell KP, Mori Y Genetic analyses have revealed an association between the gene encoding the Rab3A-interacting molecule (RIM1) and the autosomal dominant cone-rod dystrophy CORD7. However, the pathogenesis of CORD7 remains unclear. We recently revealed that RIM1 regulates voltage-dependent Ca(2+) channel (VDCC) currents and anchors neurotransmitter-containing vesicles to VDCCs, thereby controlling neurotransmitter release. We demonstrate here that the mouse RIM1 arginine-to-histidine substitution (R655H), which corresponds to the human CORD7 mutation, modifies RIM1 function in regulating VDCC currents elicited by the P/Q-type Ca(v)2.1 and L-type Ca(v)1.4 channels. Thus, our data can raise an interesting possibil... Channels journals http://www.medworm.com/rss/comments.php?id=1757277 Tue, 01 May 2007 04:00:00 +0100 1757277 http://www.medworm.com/index.php?rid=1757276&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690028%26dopt%3DAbstract Authors: McGahon MK, Zhang X, Scholfield CN, Curtis TM, McGeown JG Diabetic retinopathy is an important cause of visual loss. Functional abnormalities including vasoconstriction precede structural changes. Using the streptozotocin-model of diabetes in rats, we have identified downregulation of the beta1 subunit of the BK channel in arteriole myocytes as a possible molecular mechanism underlying these early changes. BKbeta1 mRNA levels were reduced as early as one month after induction of diabetes, and BK Ca(2+)-sensitivity and caffeine-evoked BK currents were reduced at three months. This effect appears to be selective for the regulatory subunit, as BKalpha subunit expression was not altered at the mRNA level, and voltage-activated BK currents were unaltered. No changes were seen in vo... Channels journals http://www.medworm.com/rss/comments.php?id=1757276 Tue, 01 May 2007 04:00:00 +0100 1757276 http://www.medworm.com/index.php?rid=1757275&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690029%26dopt%3DAbstract Authors: Kucheryavykh YV, Pearson WL, Kurata HT, Eaton MJ, Skatchkov SN, Nichols CG Inward rectifier K(+) (Kir) channels are expressed in multiple neuronal and glial cells. Recent studies have equated certain properties of exogenously expressed Kir4.1 channels with those of native K(+) currents in brain cells, as well as demonstrating the expression of Kir4.1 subunits in these tissues. There are nagging problems however with assigning native currents to Kir4.1 channels. One major concern is that in many native tissues, the putatively correlated currents show much weaker rectification than typically reported for cloned Kir4.1 channels. We have now examined the polyamine-dependence of Kir4.1 channels expressed at high density in Cosm6 cells, using inside-out membrane patches. The experim... Channels journals http://www.medworm.com/rss/comments.php?id=1757275 Tue, 01 May 2007 04:00:00 +0100 1757275 http://www.medworm.com/index.php?rid=1757274&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690030%26dopt%3DAbstract Authors: Krafte DS, Chapman M, Marron B, Atkinson R, Liu Y, Ye F, Curran M, Kort M, Jarvis MF Sodium channels are key proteins in regulating neuronal excitability and accumulating data suggest that specific subtypes of voltage-dependent sodium channels are important in signaling various types of pain. Consistent with this theme, Jarvis et al.(7) recently reported the identification of a subtype-selective Na(v)1.8 blocker that was active in several pre-clinical models of pain. During the course of these studies compounds were also identified that showed large differences in potency when tested on Na(v)1.8 channels from different species. This addendum illustrates one of these compounds along with the potency correlation between recombinant and native tetrodotoxin-resistant sodium channe... Channels journals http://www.medworm.com/rss/comments.php?id=1757274 Tue, 01 May 2007 04:00:00 +0100 1757274 http://www.medworm.com/index.php?rid=1757273&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690031%26dopt%3DAbstract Authors: Kato N, Akai M, Zulkifli L, Matsuda N, Kato Y, Goshima S, Hazama A, Yamagami M, Guy HR, Uozumi N Studies suggest that Ktr/Trk/HKT-type transporters have evolved from multiple gene fusions of simple K(+) channels of the KcsA type into proteins that span the membrane at least eight times. Several positively charged residues are present in the eighth transmembrane segment, M2(D), in the transporters but not K(+) channels. Some models of ion transporters require a barrier to prevent free diffusion of ions down their electrochemical gradient, and it is possible that the positively charged residues within the transporter pore may prevent transporters from being channels. Here we studied the functional role of these positive residues in three Ktr/Trk/HKT-type transporters (Synechocys... Channels journals http://www.medworm.com/rss/comments.php?id=1757273 Tue, 01 May 2007 04:00:00 +0100 1757273 http://www.medworm.com/index.php?rid=1757272&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690032%26dopt%3DAbstract Authors: Hosaka Y, Iwata M, Kamiya N, Yamada M, Kinoshita K, Fukunishi Y, Tsujimae K, Hibino H, Aizawa Y, Inanobe A, Nakamura H, Kurachi Y Chemicals and toxins are useful tools to elucidate the structure-function relationship of various proteins including ion channels. The HERG channel is blocked by many compounds and this may cause life-threatening cardiac arrhythmia. Besides block, some chemicals such as the class III anti-arrhythmic agent nifekalant stimulate HERG at low potentials by shifting its activation curve towards hyperpolarizing voltages. This is called "facilitation". Here, we report mutations and simulations analyzing the association between nifekalant and channel pore residues for block and facilitation. Alanine-scanning mutagenesis was performed in the pore region of HE... Channels journals http://www.medworm.com/rss/comments.php?id=1757272 Tue, 01 May 2007 04:00:00 +0100 1757272 http://www.medworm.com/index.php?rid=1757271&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690033%26dopt%3DAbstract Authors: Foulkes T, Wood JN Avoidance of cold pain is an important survival mechanism. Intriguingly, whilst cooling can cause numbness, damage sensing mechanisms still seem to operate at low temperatures, and pain can be perceived from cooled damaged tissue. Recent studies have identified two cold-activated Transient Receptor Potential (TRP) channels present in sensory neurons as transducers of cold stimuli. TRPM8 seems to mediate responses to cooling whilst TRPA1 is activated, possibly indirectly, by more extreme cold conditions. The existence of cold-responsive neurons that do not express these channels suggests that other transducers of cold stimuli remain to be discovered. Subsequent action potential electrogenesis and probably propagation from sensory neurons innervating cold tiss... Channels journals http://www.medworm.com/rss/comments.php?id=1757271 Tue, 01 May 2007 04:00:00 +0100 1757271 http://www.medworm.com/index.php?rid=1757270&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690034%26dopt%3DAbstract Authors: Ballester LY, Vanoye CG, George AL Andersen syndrome is an autosomal dominant disorder characterized by cardiac arrhythmias, periodic paralysis and dysmorphic features. Many Andersen syndrome cases have been associated with loss-of-function mutations in the inward rectifier K(+) channel Kir2.1 encoded by KCNJ2. Using engineered concatenated tetrameric channels we determined the mechanism for dominant loss-of-function associated with a trafficking-competent missense mutation, Kir2.1-T74A. This mutation alters a conserved threonine residue in an N-terminal domain analogous to the slide helix identified in the structure of a bacterial inward rectifier. Incorporation of a single mutant subunit in channel tetramers was sufficient to cause a selective impairment of whole-cell outwar... Channels journals http://www.medworm.com/rss/comments.php?id=1757270 Tue, 01 May 2007 04:00:00 +0100 1757270 http://www.medworm.com/index.php?rid=1757244&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18702192%26dopt%3DAbstract Authors: Soldatov NM, Weiss JN A three-day International Symposium entitled "Principles of Calcium Signaling" organized by James N. Weiss, Yale E. Goldman, Stéphane Hatem, Lars Cleemann and Nikolai M. Soldatov in honor of the research contributions of Professor Martin Morad was held at the Mount Desert Island Biological Laboratory, Salisbury Cove, Maine. Support for this meeting was provided in part by GlaxoSmithKline, Leica Microsystems, Nikon Corp., St. Jude Medical, Inc., UCLA Cardiac Arrhythmia Center, Dr. Donald S. Orkand, Bob Hillis Family and OML, and Mount Desert Island Biological Laboratory. The symposium featured sessions on Cardiac physiology, Ion channels and Calcium signaling. PMID: 18702192 [PubMed - in process] (Source: Channels) Channels journals http://www.medworm.com/rss/comments.php?id=1757244 Tue, 01 May 2007 04:00:00 +0100 1757244 http://www.medworm.com/index.php?rid=1757288&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690016%26dopt%3DAbstract Authors: Altimimi HF, Schnetkamp PP The most numerous Ca2+ extrusion protein family, in terms of distinct genes, is the SLC24 gene family of Na+/Ca2+-K+ exchangers (NCKX). Five distinct gene products have been identified, mostly from specific animal excitable tissues such as neurons and smooth muscle, but also in places like skin pigment epithelium, signifying that NCKX proteins may play very specific roles, related to Ca2+ homeostasis, in these tissues. However, progress in elucidating the specific physiological roles of NCKX proteins has been slow in coming, largely because of challenges relating to isolating the activity of these proteins in their native tissues. Herein, we provide an overview of NCKX protein functional characteristics, highlighting properties that are unique and us... Channels journals http://www.medworm.com/rss/comments.php?id=1757288 Thu, 01 Mar 2007 05:00:00 +0100 1757288 http://www.medworm.com/index.php?rid=1757287&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690017%26dopt%3DAbstract Authors: Duret G, Simonet V, Delcour AH The outer membrane of Gram-negative bacteria contains porins, large pore-forming proteins which allow the traffic of hydrophilic compounds between the external medium and the periplasm. The oral mode of infection of Vibrio cholerae, the agent of cholera, implies that the bacteria must adapt to severe changes in the environment, such as acidic pH and the presence of bile. Because of their localization and the regulation of their expression in response to these external factors, the OmpU and OmpT porins of V. cholerae are thought to be involved in the adaptation of the bacteria to the host environment. Using patch clamp and planar lipid bilayer electrophysiology, we assessed the effect of pH on the channel properties of OmpU and OmpT. OmpT does not... Channels journals http://www.medworm.com/rss/comments.php?id=1757287 Thu, 01 Mar 2007 05:00:00 +0100 1757287 http://www.medworm.com/index.php?rid=1757286&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690018%26dopt%3DAbstract In conclusion, these results represent the first demonstration for a role of the NH2-terminus in the second messenger-dependent regulation of hIK1 and, in combination with our previous findings, suggest that this regulation is dependent upon a close NH2/C-terminal association. PMID: 18690018 [PubMed - in process] (Source: Channels) Channels journals http://www.medworm.com/rss/comments.php?id=1757286 Thu, 01 Mar 2007 05:00:00 +0100 1757286 http://www.medworm.com/index.php?rid=1757285&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690019%26dopt%3DAbstract Authors: Keselman I, Fribourg M, Felsenfeld DP, Logothetis DE A large number of ion channels maintain their activity through direct interactions with phosphatidylinositol bisphosphate (PIP2). For such channels, hydrolysis of PIP2 causes current inhibition. It has become controversial whether the inhibitory effects on channel activity represent direct effects of PIP2 hydrolysis or of downstream PKC action. We studied Phospholipase C (PLC)-dependent inhibition of G protein-activated inwardly rectifying K+ (Kir3) channels. By monitoring simultaneously channel activity and PIP2 hydrolysis, we determined that both direct PIP2 depletion and PKC actions contribute to Kir3 current inhibition. We show that the PKC-induced effects strongly depend on PIP2 levels in the membrane. At the same time,... Channels journals http://www.medworm.com/rss/comments.php?id=1757285 Thu, 01 Mar 2007 05:00:00 +0100 1757285 http://www.medworm.com/index.php?rid=1757284&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690020%26dopt%3DAbstract Authors: Liang Y, Tavalin SJ L-type calcium channels (Ca(v)1.1-Ca(v)1.4) link Ca(2+) influx to membrane depolarization and serve a critical role in regulating membrane excitability, muscle contraction, hormone secretion, and gene transcription. In many tissues, L-type calcium channel activity (Ca(v)1.1 and Ca(v)1.2) is enhanced by transmitters and hormones that activate the cAMP-dependent protein kinase (PKA), which is largely thought to be mediated via phosphorylation of the pore forming alpha subunit. However, the ability of PKA to regulate Ca(v)1.3 and the sites contributing to effective modulation of channel activity remains to be established. Using HEK 293 cells, we demonstrate that currents carried by the long C-terminal splice variant of Ca(v)1.3 (Ca(v)1.3L) are selectively enha... Channels journals http://www.medworm.com/rss/comments.php?id=1757284 Thu, 01 Mar 2007 05:00:00 +0100 1757284 http://www.medworm.com/index.php?rid=1757283&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690021%26dopt%3DAbstract Authors: Lopes CM, Remon JI, Matavel A, Sui JL, Keselman I, Medei E, Shen Y, Rosenhouse-Dantsker A, Rohacs T, Logothetis DE Neurotransmitter and hormone regulation of cellular function can result from a concomitant stimulation of different signaling pathways. Signaling cascades are strongly regulated during disease and are often targeted by commonly used drugs. Crosstalk of different signaling pathways can have profound effects on the regulation of cell excitability. Members of all the three main structural families of potassium channels: inward-rectifiers, voltage-gated and 2-P domain, have been shown to be regulated by direct phosphorylation and Gq-coupled receptor activation. Here we test members of each of the three families, Kir3.1/Kir3.4, KCNQ1/KCNE1 and TREK-1 channels, all of w... Channels journals http://www.medworm.com/rss/comments.php?id=1757283 Thu, 01 Mar 2007 05:00:00 +0100 1757283 http://www.medworm.com/index.php?rid=1757282&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690022%26dopt%3DAbstract Authors: Richards MW, Leroy J, Pratt WS, Dolphin AC Ca(v)beta subunits of voltage-gated calcium channels contain two conserved domains, a src-homology-3 (SH3)-domain and a guanylate kinase-like (GK)-domain. The SH3-domain is split, with its final (fifth) beta-strand separated from the rest of the domain by an intervening sequence termed the HOOK-domain, whose sequence varies between Ca(v)beta subunits. Here we have been guided by the recent structural studies of Ca(v)beta subunits in the design of specific truncated constructs, with the goal of investigating the role of the HOOK-domain of Ca(v)beta subunits in the modulation of inactivation of N-type calcium channels. We have coexpressed the beta subunit constructs with Ca(v)2.2 and alpha(2)delta-2, using the N-terminally palmitoylated... Channels journals http://www.medworm.com/rss/comments.php?id=1757282 Thu, 01 Mar 2007 05:00:00 +0100 1757282 http://www.medworm.com/index.php?rid=1757281&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18690023%26dopt%3DAbstract Authors: Park KS, Mohapatra DP, Trimmer JS The K(v)2.1 potassium channel plays an important role in regulating membrane excitability and is highly phosphorylated in mammalian neurons. Our previous results showed that variable phosphorylation of K(v)2.1 at multiple sites allows graded activity-dependent regulation of channel gating. Our previous studies also found functional differences between recombinant K(v)2.1 channels expressed in HEK293 cells and COS-1 cells that were eliminated upon complete dephosphorylation of K(v)2.1. To better understand how phosphorylation affects K(v)2.1 gating in HEK293 and COS-1 cells we used stable isotope labeling by amino acids in cell culture (SILAC) and mass spectrometry to determine the level of phosphorylation at one newly and thirteen previously i... Channels journals http://www.medworm.com/rss/comments.php?id=1757281 Thu, 01 Mar 2007 05:00:00 +0100 1757281 http://www.medworm.com/index.php?rid=1757245&cid=s_37906_67_f&fid=37906&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18700299%26dopt%3DAbstract Authors: Davies LA, Barrett PQ PMID: 18700299 [PubMed - in process] (Source: Channels) Channels journals http://www.medworm.com/rss/comments.php?id=1757245 Thu, 01 Mar 2007 05:00:00 +0100 1757245