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 'Journal of Molecular and Cellular Cardiology' source. Thu, 18 Mar 2010 16:54:49 +0100 http://www.medworm.com/index.php?rid=3350133&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282810000507%2Fabstract%3Frss%3Dyes (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350133 Wed, 10 Mar 2010 18:21:38 +0100 3350133 http://www.medworm.com/index.php?rid=3350164&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228281000009X%2Fabstract%3Frss%3Dyes The order of authors should appear as it does above. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350164 Mon, 15 Feb 2010 00:00:00 +0100 3350164 http://www.medworm.com/index.php?rid=3258696&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282810000179%2Fabstract%3Frss%3Dyes (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3258696 Wed, 10 Feb 2010 17:01:48 +0100 3258696 http://www.medworm.com/index.php?rid=3350145&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282810000143%2Fabstract%3Frss%3Dyes Abstract: Biglycan, a proteoglycan component of extracellular matrix, has been suspected to contribute to the development of atherosclerosis, but overexpression of biglycan in transgenic mice has been shown to induce cardioprotective genes including nitric oxide (NO) synthases in the heart. Therefore, here we hypothesized if exogenous administration of biglycan exerts cytoprotection. Primary cardiomyocytes from neonatal rats were subjected to 150 min hypoxia and 2 h reoxygenation. Mortality of cardiomyocytes was dose-dependently attenuated by pretreatment with 1–100 nM biglycan. Biglycan enhanced eNOS mRNA and protein, and significantly increased NO content of cardiomyocytes. The NO synthase inhibitor l-nitro-arginine-methyl-ester significantly attenuated the cytoprotective effect of b... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350145 Thu, 21 Jan 2010 00:00:00 +0100 3350145 http://www.medworm.com/index.php?rid=3350142&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282810000106%2Fabstract%3Frss%3Dyes Abstract: Heart failure affects nearly 6 million Americans, with a half-million new cases emerging each year. Whereas up to 50% of heart failure patients die of arrhythmia, the diverse mechanisms underlying heart failure-associated arrhythmia are poorly understood. As a consequence, effectiveness of antiarrhythmic pharmacotherapy remains elusive. Here, we review recent advances in our understanding of heart failure-associated molecular events impacting the electrical function of the myocardium. We approach this from an anatomical standpoint, summarizing recent insights gleaned from pre-clinical models and discussing their relevance to human heart failure. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350142 Thu, 21 Jan 2010 00:00:00 +0100 3350142 http://www.medworm.com/index.php?rid=3350137&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282810000131%2Fabstract%3Frss%3Dyes The epicardium is a connective tissue membrane covering the heart and is continuous with the investing pericardium. The epicardium consists of a layer of fibroelastic tissue merging with the endomysium of the underlying cardiac muscle and a layer of superficial mesothelial membrane (visceral layer of serous pericardium). The pericardium also consists of two layers, outer fibroelastic connective tissue layer and inner mesothelial membrane pericardium (parietal layer of serous pericardium), and the parietal and visceral serous pericardia are continuous structures. Physical properties and physiological function of the pericardium were extensively studied in the 1980s, and it has been shown that the pericardium restrains left ventricular filling and enhances diastolic ventricular interaction (... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350137 Thu, 21 Jan 2010 00:00:00 +0100 3350137 http://www.medworm.com/index.php?rid=3189007&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809005252%2Fabstract%3Frss%3Dyes (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189007 Wed, 20 Jan 2010 17:09:58 +0100 3189007 http://www.medworm.com/index.php?rid=3350144&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282810000088%2Fabstract%3Frss%3Dyes Abstract: The phosphatase vs. kinase equilibrium plays a critical role in the regulation of myocardial contractility. Previous studies have demonstrated that peroxynitrite exerts a biphasic effect on cardiomyocyte contraction, such that high peroxynitrite reduced β-adrenergic-stimulated myocyte contraction by inducing the dephosphorylation of phospholamban (PLB) via phosphatase activation. Conversely, low peroxynitrite increased basal and β-adrenergic-stimulated contraction also through a PLB-dependent mechanism. However, previous studies have not elucidated the mechanism underlying the positive effects of low peroxynitrite on myocyte contraction. In the current study, we examined the phosphatase vs. kinase equilibrium as a potential mechanism underlying the positive effects of peroxynit... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350144 Mon, 18 Jan 2010 00:00:00 +0100 3350144 http://www.medworm.com/index.php?rid=3350157&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282810000076%2Fabstract%3Frss%3Dyes This study investigated the relationship between the NADPH oxidase system, age-related cardiac remodeling and its underlying mechanisms. We studied male Fisher 344 cross Brown Norway rats aged 2 months (young rats), 8 months (young adult rats) or 30 months (old rats). Aging-dependent increases in blood pressure, cardiomyocyte area, coronary artery remodeling and cardiac fibrosis were associated with increased myocardial NADPH oxidase activity attributable to the Nox2 isoform. These changes were accompanied by evidence of local RAAS activation, increased expression of connective tissue growth factor (CTGF) and TGF-β1, and a significant activation of MMP-2 and MT1-MMP. The changes in old rats were replicated in 8 month old rats that were chronically treated with angiotensin II for 28 days. ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350157 Fri, 15 Jan 2010 00:00:00 +0100 3350157 http://www.medworm.com/index.php?rid=3350161&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809005483%2Fabstract%3Frss%3Dyes We read with great interest the recent Point/Counterpoint article by Lakatta and DiFrancesco on the relative role of the hyperpolarization-activated “funny current” If vs. that of intracellular Ca2+ cycling in controlling the normal pacemaker cell automaticity . In this article, it is argued by Dr. Lakatta, referring to experimental data from our laboratory , that “the extent to which If becomes activated during diastolic depolarization in primary sinoatrial node cells must be low, in general, but especially in humans.” We would like to comment on the suggestion that the funny current is less important in the human sinoatrial (SA) node than in rabbit. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350161 Mon, 11 Jan 2010 00:00:00 +0100 3350161 http://www.medworm.com/index.php?rid=3350154&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809005690%2Fabstract%3Frss%3Dyes In conclusion, IP CD117/Sca-1+ murine BM-MSCs display robust cardiac muscle lineage development that can be induced independent of AZA but is diminished under higher serum concentrations. Furthermore, temporal changes in calcium kinetics commensurate with increased cTnT expression suggest progressive maturation of a cardiac muscle lineage. Enrichment with CD117/Sca-1 to establish lineage commitment followed by DHPR-α2 in lineage developing cells may enhance the therapeutic potential of these cells for transplantation. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350154 Thu, 07 Jan 2010 00:00:00 +0100 3350154 http://www.medworm.com/index.php?rid=3145778&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809005094%2Fabstract%3Frss%3Dyes With their propensity to lead to sudden death, cardiac arrhythmias are a major clinical problem. They also represent an exciting medical challenge which needs the association of fundamental molecular and cell physiologists and cardiologists to unravel the underlying arrhythmogenic mechanisms and to imagine new therapeutic approaches. Since the development of the patch-clamp technique some 30 years ago, an incredibly large amount of knowledge has been obtained. After biophysical dissection of ion currents, the inputs from molecular biology and genetics have allowed the identification and functional description of many proteins responsible for the channel function. In this issue of Journal of Molecular and Cellular Cardiology a series of review articles and original papers highlight the lat... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145778 Fri, 01 Jan 2010 00:00:00 +0100 3145778 http://www.medworm.com/index.php?rid=3145777&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809005033%2Fabstract%3Frss%3Dyes (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145777 Fri, 01 Jan 2010 00:00:00 +0100 3145777 http://www.medworm.com/index.php?rid=3350153&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809005586%2Fabstract%3Frss%3Dyes Abstract: Decoding of the bioenergetic signature underlying embryonic stem cell cardiac differentiation has revealed a mandatory transformation of the metabolic infrastructure with prominent mitochondrial network expansion and a distinctive switch from glycolysis to oxidative phosphorylation. Here, we demonstrate that despite reduction in total glycolytic capacity, stem cell cardiogenesis engages a significant transcriptome, proteome, as well as enzymatic and topological rearrangement in the proximal, medial, and distal modules of the glycolytic pathway. Glycolytic restructuring was manifested by a shift in hexokinase (Hk) isoforms from Hk-2 to cardiac Hk-1, with intracellular and intermyofibrillar localization mapping mitochondrial network arrangement. Moreover, upregulation of cardiac-sp... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350153 Thu, 31 Dec 2009 00:00:00 +0100 3350153 http://www.medworm.com/index.php?rid=3350163&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809005197%2Fabstract%3Frss%3Dyes In their letter to the Editor (the Letter ) Verkerk and Wilders utilized numerical modeling to ascertain the relative importance of the funny current (If) in human versus rabbit sinoatrial node. The main thrust of the model simulations in the Letter is that in both species If during DD is close to Inet defined as (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350163 Mon, 28 Dec 2009 00:00:00 +0100 3350163 http://www.medworm.com/index.php?rid=3350162&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809005203%2Fabstract%3Frss%3Dyes In their Letter to the Editor, Verkerk and Wilders make the point that the funny current has the same relevance in rabbit and human sinoatrial nodes, based on a comparison between experimental and numerical reconstruction data in the two tissues. In essence, they point out that it is not true, as stated by E. Lakatta (counterpoint of Ref. ), that If is less important in human than in rabbit pacemaker cells because it is small, since though smaller than in the rabbit, its size is perfectly compatible with the lower-rate activity recorded in humans. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350162 Mon, 28 Dec 2009 00:00:00 +0100 3350162 http://www.medworm.com/index.php?rid=3350150&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809005227%2Fabstract%3Frss%3Dyes Abstract: Apelin, a ligand of the G protein-coupled putative angiotensin II-like receptor (APJ-R), exerts strong vasodilating, cardiac inotropic and chronotropic actions. Its expression is highly up-regulated during heart failure. Apelin also increases cardiac conduction speed and excitability. While our knowledge of apelin cardiovascular actions is growing, our understanding of the physiological mechanisms behind the cardiac effects remains limited. We tested the effects of apelin on the cardiac sodium current (INa) using patch clamp technique on cardiac myocytes acutely dissociated from dog ventricle. We found that apelin-13 and apelin-17 increased peak INa by 39% and 61% and shifted its mid-activation potential by −6.8±0.6 mV and −17±1 mV respectively thus increasing channel ope... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350150 Mon, 28 Dec 2009 00:00:00 +0100 3350150 http://www.medworm.com/index.php?rid=3350134&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004970%2Fabstract%3Frss%3Dyes Fuelled by obesity, hypertension, diabetes, and an aging population, heart failure (HF) is increasingly common in the Western population. Its pathophysiology reflects the complex and multifactorial background, and involvement of neurohormones, cytokines and oxidative stress in an interrelated network of pathways and players. Linking gene expression to loss of function in HF has helped to unravel many of these players, such as the central role of tumor necrosis factor-α, and provided successful treatment targets, like the renin–angiotensin system. Moreover, it helped to link the typical (mal)adaptive myocardial phenotypes, such as hypertrophied and atrophied heart, and insulin resistance and cardiac metabolic maladaptation . For instance, several lines of evidence suggest that a diabetic... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350134 Fri, 18 Dec 2009 00:00:00 +0100 3350134 http://www.medworm.com/index.php?rid=3350136&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004969%2Fabstract%3Frss%3Dyes Human heart tissue is difficult to obtain. Its procurement depends upon access to a center at which heart transplants or ventricular assist device implantations occur as well as a willingness to serve science at odd hours and on short notice. As if these barriers were not sufficiently discouraging to the would-be translational investigator, there are specific and thorny challenges associated with isolating, culturing, and studying human cardiomyocytes. Even observations made in meticulously procured human myocardium and cardiomyocytes are subject to limitations, as outlined in a thoughtful review published previously in this journal . Thus, the cardiovascular research community relies largely upon animal models to study myocardial disease, the most common of which is the genetically altere... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350136 Mon, 14 Dec 2009 00:00:00 +0100 3350136 http://www.medworm.com/index.php?rid=3350135&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004982%2Fabstract%3Frss%3Dyes The controversial discussion as to whether the failing heart is “an energy starved organ” is an old one. In 1939 Herrmann and Dechard first described a significant decrease in Cr in the failing heart . It was confirmed later by in vivo Nuclear Magnetic Resonance (NMR)-spectroscopy that the PCr concentration decreases in failing myocardium, preceding and exceeding the loss of ATP . While resting ATP levels are maintained, the CP/ATP ratio as a measure of energy reserve is reduced in failing myocardium. Cr is produced in the liver and kidneys and taken up by a specific myocardial plasma-membrane Cr transporter . In failing myocardium, the Cr transporter is diminished which in part explains a decrease in Cr . Further, the activity of mitochondrial and myofibrillar CK decreases in heart fa... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350135 Mon, 14 Dec 2009 00:00:00 +0100 3350135 http://www.medworm.com/index.php?rid=3350143&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004878%2Fabstract%3Frss%3Dyes Abstract: Among the players involved in Ca2+ homeostasis in heart tissue are SERCA (sarco/endoplasmic reticulum Ca2+ ATPase)-type Ca2+ pumps. Until recently, human heart was known to coexpress major SERCA2a and minor SERCA2b isoforms. Here, we will summarize data showing that nonfailing human heart is equipped with an increasing variety of SERCA isoforms comprised new SERCA2 (ATP2A2) and SERCA3 (ATP2A3) gene products. The novel 3′-ends of the human SERCA2 and -3 genes, the corresponding mRNAs and the carboxyl termini of the SERCA2a-2c and SERCA3a-3f isoforms will be presented. The intrinsic characteristics and effects on cellular Ca2+ homeostasis of the SERCA2 and SERCA3 recombinant isoforms will be summarized. Evidence for the expression of SERCA2c and SERCA3a, -3d, and -3f mRNAs and/or... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350143 Mon, 07 Dec 2009 00:00:00 +0100 3350143 http://www.medworm.com/index.php?rid=3350141&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004830%2Fabstract%3Frss%3Dyes In conclusion, myocardial infarction reactivates an embryonic program in epicardial c-kit+ cells; soluble factors released in the pericardial fluids following myocardial necrosis may play a role in this process. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350141 Mon, 07 Dec 2009 00:00:00 +0100 3350141 http://www.medworm.com/index.php?rid=3189018&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228280900491X%2Fabstract%3Frss%3Dyes Abstract: The cardiac sodium channel (SCN5A, NaV1.5) is a key determinant of electrical impulse conduction in cardiac tissue. Acute myocardial infarction leads to diminished sodium channel availability, both because of decreased channel expression and because of greater inactivation of channels already present. Myocardial infarction leads to significant increases in reactive oxygen species and their downstream effectors including lipoxidation products. The effects of reactive oxygen species on NaV1.5 function in whole hearts can be modeled in cultured myocytes, where oxidants shift the availability curve of INa to hyperpolarized potentials, decreasing cardiac sodium current at the normal activation threshold. We recently examined potential mediators of the oxidant-induced inactivation and ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189018 Mon, 07 Dec 2009 00:00:00 +0100 3189018 http://www.medworm.com/index.php?rid=3350149&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004854%2Fabstract%3Frss%3Dyes Abstract: Our recent studies have indicated that acetylcholine (ACh) protects cardiomyocytes from prolonged hypoxia through activation of the PI3K/Akt/HIF-1α/VEGF pathway and that cardiomyocyte-derived VEGF promotes angiogenesis in a paracrine fashion. These results suggest that a cholinergic system plays a role in modulating angiogenesis. Therefore, we assessed the hypothesis that the cholinergic modulator donepezil, an acetylcholinesterase inhibitor utilized in Alzheimer's disease, exhibits beneficial effects, especially on the acceleration of angiogenesis. We evaluated the effects of donepezil on angiogenic properties in vitro and in vivo, using an ischemic hindlimb model of α7 nicotinic receptor-deleted mice (α7 KO) and wild-type mice (WT). Donepezil activated angiogenic signals, i.... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350149 Fri, 04 Dec 2009 00:00:00 +0100 3350149 http://www.medworm.com/index.php?rid=3350148&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004866%2Fabstract%3Frss%3Dyes Abstract: We have previously proposed that the heterogeneous collapse of mitochondrial inner membrane potential (ΔΨm) during ischemia and reperfusion contributes to arrhythmogenesis through the formation of metabolic sinks in the myocardium, wherein clusters of myocytes with uncoupled mitochondria and high KATP current levels alter electrical propagation to promote reentry. Single myocyte studies have also shown that cell-wide ΔΨm depolarization, through a reactive oxygen species (ROS)-induced ROS release mechanism, can be triggered by global depletion of the antioxidant pool with diamide, a glutathione oxidant. Here we examine whether diamide causes mitochondrial depolarization and promotes arrhythmias in normoxic isolated perfused guinea pig hearts. We also investigate whether stabil... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350148 Fri, 04 Dec 2009 00:00:00 +0100 3350148 http://www.medworm.com/index.php?rid=3350147&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004921%2Fabstract%3Frss%3Dyes Abstract: There is clinical evidence to suggest that impaired myocardial glucose uptake contributes to the pathogenesis of hypertrophic, insulin-resistant cardiomyopathy. The goal of this study was to determine whether cardiac deficiency of the insulin-sensitive glucose transporter, GLUT4, has deleterious effect on cardiomyocyte excitation–contraction coupling. Cre-Lox mouse models of cardiac GLUT4 knockdown (KD, 85% reduction) and knockout (KO, >95% reduction), which exhibit similar systemic hyperinsulinemic and hyperglycemic states, were investigated. The Ca2+ current (ICa) and Na+–Ca2+ exchanger (NCX) fluxes, Na+–H+ exchanger (NHE) activity, and contractile performance of GLUT4-deficient myocytes was examined using whole-cell patch-clamp, epifluorescence, and imaging techniques. G... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350147 Fri, 04 Dec 2009 00:00:00 +0100 3350147 http://www.medworm.com/index.php?rid=3350152&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004908%2Fabstract%3Frss%3Dyes Abstract: Increased cyclic GMP from enhanced synthesis or suppressed catabolism (e.g. PDE5 inhibition by sildenafil, SIL) activates protein kinase G (PKG) and blunts cardiac pathological hypertrophy. Suppressed calcineurin (Cn)-NFAT (nuclear factor of activated T-cells) signaling appears to be involved, though it remains unclear how this is achieved. One potential mechanism involves activation of Cn/NFAT by calcium entering via transient receptor potential canonical (TRPC) channels (notably TRPC6). Here, we tested the hypothesis that PKG blocks Cn/NFAT activation by modifying and thus inhibiting TRPC6 current to break the positive feedback loop involving NFAT and NFAT-dependent TRPC6 upregulation. TRPC6 expression rose with pressure-overload in vivo, and angiotensin (ATII) or endothelin (E... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350152 Thu, 03 Dec 2009 00:00:00 +0100 3350152 http://www.medworm.com/index.php?rid=3189019&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004842%2Fabstract%3Frss%3Dyes In conclusion, HSP72 is not increased in heart failure because HSF activity is not changed; increased expression of HSP60 may be driven by NFκB activation. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189019 Mon, 30 Nov 2009 00:00:00 +0100 3189019 http://www.medworm.com/index.php?rid=3189017&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004829%2Fabstract%3Frss%3Dyes In conclusion, this work has provided insight into the intracellular signaling pathways and transcription factors regulating Ncx1 gene expression in a chronically β-AR-stimulated heart. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189017 Mon, 30 Nov 2009 00:00:00 +0100 3189017 http://www.medworm.com/index.php?rid=3350140&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004817%2Fabstract%3Frss%3Dyes Abstract: Mutations in LMNA, the gene encoding the nuclear membrane proteins, lamins A and C, produce cardiac and muscle disease. In the heart, these autosomal dominant LMNA mutations lead to cardiomyopathy frequently associated with cardiac conduction system disease. Herein, we describe a patient with the R374H missense variant in nesprin-1α, a protein that binds lamin A/C. This individual developed dilated cardiomyopathy requiring cardiac transplantation. Fibroblasts from this individual had increased expression of nesprin-1α and lamins A and C, indicating changes in the nuclear membrane complex. We characterized mice lacking the carboxy-terminus of nesprin-1 since this model expresses nesprin-1 without its carboxy-terminal KASH domain. These Δ/ΔKASH mice have a normally assembled bu... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350140 Fri, 27 Nov 2009 00:00:00 +0100 3350140 http://www.medworm.com/index.php?rid=3189009&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004805%2Fabstract%3Frss%3Dyes Ca2+ dependent arrhythmias were first appreciated as a distinct cellular signaling process when triggered extrasystoles were linked to abnormally elevated Ca2+ concentrations in the sarcoplasmic reticulum (SR) store. Thus large elevations of [Ca2+]SR (or “SR Ca2+ overload”) were shown to be linked to both early and delayed afterdepolarizations . However, only recently have changes in Ca2+ sparks, the primary elemental SR Ca2+ release events, become associated with a molecular mechanism of SR Ca2+ leak and arrhythmogenesis (A). Specifically, missense mutations of the cardiac ryanodine receptor (RyR2) have been associated with an increased Ca2+ spark frequency and cell-wide arrhythmogenic Ca2+ waves that could underlie extrasystoles and lead to arrhythmias . However, the molecular and ph... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189009 Fri, 20 Nov 2009 00:00:00 +0100 3189009 http://www.medworm.com/index.php?rid=3189020&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004787%2Fabstract%3Frss%3Dyes This study was designed to examine the impact of the antioxidant metallothionein (MT) on lipopolysaccharide (LPS)-induced cardiac contractile and intracellular Ca2+ dysfunction, oxidative stress, endoplasmic reticulum (ER) stress and autophagy. Mechanical and intracellular Ca2+ properties were examined in hearts from FVB and cardiac-specific MT overexpression mice treated with LPS. Oxidative stress, activation of mitogen-activated protein kinase pathways (ERK, JNK and p38), ER stress, autophagy and inflammatory markers iNOS and TNFα were evaluated. Our data revealed enlarged end systolic diameter, decreased fractional shortening, myocyte peak shortening and maximal velocity of shortening/relengthening as well as prolonged duration of relengthening in LPS-treated FVB mice associated with r... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189020 Mon, 16 Nov 2009 00:00:00 +0100 3189020 http://www.medworm.com/index.php?rid=3350156&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228280900474X%2Fabstract%3Frss%3Dyes We report that ethanol preconditioning requires PKCɛ, whereas direct activation of ALDH2 reduces infarct size in both wild type and PKCɛ knockout hearts. Our data suggest that ALDH2 is downstream of PKCɛ in ethanol preconditioning and that direct activation of ALDH2 can circumvent the requirement of PKCɛ to induce cytoprotection. We also report that in addition to ALDH2 activation, Alda-44 prevents 4-HNE induced inactivation of ALDH2 by reducing the formation of 4-HNE-ALDH2 protein adducts. Thus, Alda-44 promotes metabolism of cytotoxic reactive aldehydes that accumulate in ischemic myocardium. Taken together, our findings suggest that direct activation of ALDH2 may represent a method of harnessing the cardioprotective effect of ethanol without the side effects associated with alcohol ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350156 Fri, 13 Nov 2009 00:00:00 +0100 3350156 http://www.medworm.com/index.php?rid=3350155&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004738%2Fabstract%3Frss%3Dyes In this study we determined the effect of these PKC isozymes in the survival of coronary endothelial cells (CVEC). We demonstrate here that serum deprivation of CVEC increased eNOS-mediated ROS levels, activated caspase-3, reduced Akt phosphorylation and cell number. Treatment with either the δPKC inhibitor, δV1-1, or the ɛPKC activator, ψɛRACK, inhibited these effects, restoring cell survival through inhibition of eNOS activity. The decrease in eNOS activity coincided with specific de-phosphorylation of eNOS at Ser1179, and eNOS phosphorylation at Thr497 and Ser116. Furthermore, δV1-1 or ψɛRACK induced physical association of eNOS with caveolin-1, an additional marker of eNOS inhibition, and restored Akt activation by inhibiting its nitration. Together our data demonstrate that (1... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350155 Fri, 13 Nov 2009 00:00:00 +0100 3350155 http://www.medworm.com/index.php?rid=3350151&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004763%2Fabstract%3Frss%3Dyes Abstract: A gene manipulated cell patch using a homologous peritoneum substrate was developed and applied after myocardial infarction to repair scarred myocardium. We genetically engineered male rat mesenchymal stem cells (MSC) using adenoviral transduction to over-express CXCR4/green fluorescent protein (GFP) (MSCCXCR4) or MSCNull or siRNA targeting CXCR4 (MSCsiRNA). Gene expression was studied by real-time quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA). Cells were cultured on excised peritoneum for 9 days. Two weeks after left anterior descending (LAD) coronary artery ligation in female hearts, the peritoneum patch was applied over the scarred myocardium, cell side down. Efficacy of engraftment was determined by presence of GFP positive cells. One month after cell ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350151 Fri, 13 Nov 2009 00:00:00 +0100 3350151 http://www.medworm.com/index.php?rid=3350139&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004726%2Fabstract%3Frss%3Dyes Abstract: Myocardial [ATP] falls in the failing heart. One potential compensatory mechanism for maintaining a near normal free energy of ATP hydrolysis (ΔG∼ATP), despite a fall in [ATP], may be the reduction of myocardial creatine (Cr). To test this, we conducted a longitudinal study using transgenic mice overexpressing cardiac Gsα, which slowly developed cardiomyopathy. Myocardial energetics measured using 31P NMR spectroscopy and isovolumic contractile performance were determined in perfused hearts isolated from 5-, 10-, 17-month-old Gsα and age-matched littermate wild type (WT) mice. In young Gsα hearts, contractile performance was enhanced with near normal cardiac energetics. With age, as contractile performance progressively decreased in Gsα hearts, [ATP] and [PCr] progressivel... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350139 Fri, 13 Nov 2009 00:00:00 +0100 3350139 http://www.medworm.com/index.php?rid=3350138&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004775%2Fabstract%3Frss%3Dyes Abstract: The metabolic phenotype of the failing heart includes a decrease in phosphocreatine and total creatine concentration [Cr], potentially contributing to contractile dysfunction. Surprisingly, in 32- week-old mice over-expressing the myocardial creatine transporter (CrT-OE), we previously demonstrated that elevated [Cr] correlates with left ventricular (LV) hypertrophy and failure. The aim of this study was to determine the temporal relationship between elevated [Cr] and the onset of cardiac dysfunction and to screen for potential molecular mechanisms. CrT-OE mice were compared with wild-type (WT) littermate controls longitudinally using cine-MRI to measure cardiac function and single-voxel 1H-MRS to measure [Cr] in vivo at 6, 16, 32, and 52 weeks of age. CrT-OE mice had elevated ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350138 Fri, 13 Nov 2009 00:00:00 +0100 3350138 http://www.medworm.com/index.php?rid=2967061&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228280900443X%2Fabstract%3Frss%3Dyes (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2967061 Fri, 06 Nov 2009 16:20:02 +0100 2967061 http://www.medworm.com/index.php?rid=3189016&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004647%2Fabstract%3Frss%3Dyes Abstract: The cytochrome P450 (CYP) epoxygenase enzymes CYP2J and CYP2C catalyze the epoxidation of arachidonic acid to epoxyeicosatrienoic acids (EETs), which are rapidly hydrolyzed to dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). It is well-established that CYP epoxygenase-derived EETs possess potent vasodilatory effects; however, the cellular effects of EETs and their regulation of various inflammatory processes have become increasingly appreciated in recent years, suggesting that the role of this pathway in the cardiovascular system extends beyond the maintenance of vascular tone. In particular, CYP epoxygenase-derived EETs inhibit endothelial activation and leukocyte adhesion via attenuation of nuclear factor-kappaB activation, inhibit hemostasis, protect a... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189016 Wed, 04 Nov 2009 00:00:00 +0100 3189016 http://www.medworm.com/index.php?rid=3350158&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004623%2Fabstract%3Frss%3Dyes In conclusion, oxidation-dependent facilitation of L-type Ca2+ channels is mediated by oxidation-dependent CaMKII activation, in which local Ca2+ increases induced by SR Ca2+ release is required. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350158 Mon, 02 Nov 2009 00:00:00 +0100 3350158 http://www.medworm.com/index.php?rid=3189027&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004593%2Fabstract%3Frss%3Dyes We appreciate the comments made by Gehmlich and coworkers but would like to stress that an in-depth discussion of MLP and its functions in cardio-mechanosensation was well beyond the scope of the editorial accompanying the elegant paper by Boateng and coworkers . Our view is that available data on MLP location and function in myocytes raise (and definitely do not rule out) the intriguing possibility that MLP is involved in stress sensing. The fact that MLP is not only found in the Z-disc (a sole Z-disc location has never been claimed), but sometimes in the I-band and also at the costamere and intercalated disk, as well as abundantly in the cytosol and nucleus, suggests that MLP could act as a signalling molecule between the sarcomere, cytosol, and other compartments of the myocyte. MLP mos... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189027 Mon, 02 Nov 2009 00:00:00 +0100 3189027 http://www.medworm.com/index.php?rid=3189026&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004635%2Fabstract%3Frss%3Dyes Dear Editor, The recent editorial by Gunkel et al. comprehensively summarizes recent advances in understanding the important roles of muscle LIM protein (MLP) in the healthy and diseased heart. However, we do not agree with the authors' conclusion that MLP is a stretch-sensing protein of the Z-disc and were surprised to see the dismissive and incorrect statements on data that we recently published . Several lines of evidence from other investigators and from our laboratories indicate that MLP is a diffuse cytoplasmic protein in the healthy myocardium and is not tightly associated with sarcomeric structures . This state of affairs makes a role for MLP as a direct sarcomeric stress sensor unlikely. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189026 Mon, 02 Nov 2009 00:00:00 +0100 3189026 http://www.medworm.com/index.php?rid=3189022&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004659%2Fabstract%3Frss%3Dyes Abstract: mAKAPβ is the scaffold for a multimolecular signaling complex in cardiac myocytes that is required for the induction of neonatal myocyte hypertrophy. We now show that the pro-hypertrophic phosphatase calcineurin binds directly to a single site on mAKAPβ that does not conform to any of the previously reported consensus binding sites. Calcineurin–mAKAPβ complex formation is increased in the presence of Ca2+/calmodulin and in norepinephrine-stimulated primary cardiac myocytes. This binding is of functional significance because myocytes exhibit diminished norepinephrine-stimulated hypertrophy when expressing a mAKAPβ mutant incapable of binding calcineurin. In addition to calcineurin, the transcription factor NFATc3 also associates with the mAKAPβ scaffold in myocytes. Calcine... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189022 Mon, 02 Nov 2009 00:00:00 +0100 3189022 http://www.medworm.com/index.php?rid=3189015&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004581%2Fabstract%3Frss%3Dyes Abstract: The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) targets a number of Ca2+ homeostatic proteins and regulates gene transcription. Many of the substrates phosphorylated by CaMKII are also substrates for protein kinase A (PKA), the best known downstream effector of β-adrenergic receptor (β-AR) signaling. While PKA and CaMKII are conventionally considered to transduce signals through separate pathways, there is a body of evidence suggesting that CaMKII is activated in response to β-AR stimulation and that some of the downstream effects of β-AR stimulation are actually mediated by CaMKII. The signaling pathway through which β-AR stimulation activates CaMKII, in parallel with or downstream of PKA, is not well-defined. This review considers the evidence for ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189015 Mon, 02 Nov 2009 00:00:00 +0100 3189015 http://www.medworm.com/index.php?rid=3189010&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004611%2Fabstract%3Frss%3Dyes Heart failure is a leading cause of morbidity and mortality and is extremely expensive to treat. Drug discovery efforts over the past 3 decades have focused predominantly on targeting “proximal” G-protein coupled receptor (GPCR) signaling and such approaches have delivered drugs that improve heart failure mortality. Nevertheless, the outlook still remains dismal, with 40% of patients being hospitalized or dying within 12 months, despite blockade of β- and α-adrenoceptors and inhibition of the renin-angiotensin system . More recently, “downstream” protein kinases have begun to attract attention as drug targets and kinase inhibitors are already having a major impact in oncology, where the biological roles of kinases were first investigated and are best understood, allowing the rati... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189010 Mon, 02 Nov 2009 00:00:00 +0100 3189010 http://www.medworm.com/index.php?rid=3189008&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228280900457X%2Fabstract%3Frss%3Dyes Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are two families of diseases caused by mutations of sarcomeric proteins. HCM is the leading cause of sudden cardiac death in young people and it is characterized by a thickening of the left ventricular wall (for review see ). DCM on the other hand shows the opposite phenotype, being characterized by ventricular wall thinning (for review see ). Interestingly, mutation of the same protein can cause either HCM or DCM depending on the exact mutation. The molecular basis for the differential phenotype (HCM vs. DCM) is not well understood; however, in this issue of the Journal of Molecular and Cellular Cardiology, Debold et al. take a large step forward in exploring this interesting question by examining the molecular effects of ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189008 Fri, 30 Oct 2009 00:00:00 +0100 3189008 http://www.medworm.com/index.php?rid=3189029&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004234%2Fabstract%3Frss%3Dyes The authors recently discovered that the representative blot of IL-6 in was incorrect. The correct representative IL-6 blot for is included below. Although the corrected representative blot did not alter the final results or the conclusions of the study, the authors express their sincere apologies to the readership for this error. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189029 Mon, 26 Oct 2009 00:00:00 +0100 3189029 http://www.medworm.com/index.php?rid=3189028&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004246%2Fabstract%3Frss%3Dyes The authors recently discovered that the representative blot of P-IкB-α offered as was not the correct blot. The appropriate blot for is included below. Although the corrected representative blot did not alter the final results or the conclusions of the study, the authors express their sincere apologies to the readership for this error. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189028 Mon, 26 Oct 2009 00:00:00 +0100 3189028 http://www.medworm.com/index.php?rid=3189023&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004271%2Fabstract%3Frss%3Dyes Abstract: There is considerable evidence to support a role for lipotoxicity in the development of diabetic cardiomyopathy, although the molecular links between enhanced saturated fatty acid uptake/metabolism and impaired cardiac function are poorly understood. In the present study, the effects of acute exposure to the saturated fatty acid, palmitate, on myocardial contractility and excitability were examined directly. Exposure of isolated (adult mouse) ventricular myocytes to palmitate, complexed to bovine serum albumin (palmitate:BSA) as in blood, rapidly reduced (by 54±4%) mean (±SEM) unloaded fractional cell shortening. The amplitudes of intracellular Ca2+ transients decreased in parallel. Current–clamp recordings revealed that exposure to palmitate:BSA markedly shortened action pot... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189023 Mon, 26 Oct 2009 00:00:00 +0100 3189023 http://www.medworm.com/index.php?rid=3189024&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004350%2Fabstract%3Frss%3Dyes Abstract: Recent studies demonstrated a role of sphingosine-1-phosphate (S1P) in the protection against the stress of ischemia/reperfusion (I/R) injury. In experiments reported here, we have investigated the signaling through the S1P cascade by FTY720, a sphingolipid drug candidate displaying structural similarity to S1P, underlying the S1P cardioprotective effect. In ex vivo rat heart and isolated sinoatrial node models, FTY720 significantly prevented arrhythmic events associated with I/R injury including premature ventricular beats, VT, and sinus bradycardia as well as A–V conduction block. Real-time PCR and Western blot analysis demonstrated the expression of the S1P receptor transcript pools and corresponding proteins including S1P1, S1P2, and S1P3 in tissues dissected from sinoatria... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189024 Thu, 22 Oct 2009 00:00:00 +0100 3189024 http://www.medworm.com/index.php?rid=3189013&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004362%2Fabstract%3Frss%3Dyes Abstract: MTK1 (MEKK4) is a mitogen-activated protein kinase kinase kinase that regulates the activity of its downstream mitogen-activated kinases, p38, and c-Jun N-terminal kinase (JNK). However, the physiological function of MTK1 in the heart remains to be determined. Here, we attempted to elucidate the function of MTK1 in the heart using in vitro and in vivo models. MTK1 was activated in the hearts of mice subjected to pressure overload-induced heart failure. Overexpression of a constitutively active mutant of MTK1 (MTK1ΔN) induced apoptosis in isolated neonatal rat cardiomyocytes, whereas a kinase domain-deleted form of MTK1 attenuated H2O2-induced apoptosis. Specific inhibitors of p38 or JNK effectively protected cardiomyocytes from MTK1ΔN-induced cell death. In mice, cardiac-specif... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189013 Wed, 21 Oct 2009 00:00:00 +0100 3189013 http://www.medworm.com/index.php?rid=3258698&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228280900426X%2Fabstract%3Frss%3Dyes Abstract: Vascular cells are very sensitive to their hemodynamic environment. Any change in blood pressure or blood flow can be sensed by endothelial and vascular smooth muscle cells and ultimately results in structural modifications within the vascular wall that accommodate the new conditions. In the case of hypertension, the increase in arterial stretch stimulates vessel thickening to normalize the tensile forces. This process requires modification of the extracellular matrix and of cell–matrix interactions, which mainly involves extracellular proteases. In hypertension, chronic exposure of the arterial wall to stretch leads to vascular remodeling, arterial stiffness and calcification, which finally affect target organ function. This review surveys how mechanical stretch regulates extr... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3258698 Mon, 19 Oct 2009 00:00:00 +0100 3258698 http://www.medworm.com/index.php?rid=3189025&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004301%2Fabstract%3Frss%3Dyes We report here that a subpopulation of cardiac mesoangioblasts, induced to differentiate in vitro into cardiomyocytes, do acquire a phenotype with specific mature pacemaker myocytes properties. These include expression of the HCN4 isoform of pacemaker (“funny”, f-) channels and connexin 45 (Cx45), as well as reduced expression of inwardly-rectifying potassium channels. Furthermore, MAB-derived myocytes form agglomerates of pacing cells displaying stable rhythmic activity, and as in native cardiac pacemaker cells, f-channel modulation by autonomic transmitters contributes to control of spontaneous rate in differentiated mesoangioblasts. These data represent the first evidence for in vitro generation of pacemaker-like myocytes from proliferating non-embryonic stem/progenitor cells. (Sour... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189025 Mon, 19 Oct 2009 00:00:00 +0100 3189025 http://www.medworm.com/index.php?rid=3189012&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004283%2Fabstract%3Frss%3Dyes Abstract: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is linked to mutations in the cardiac ryanodine receptor (RyR2) or calsequestrin. We recently found that the drug flecainide inhibits RyR2 channels and prevents CPVT in mice and humans. Here we compared the effects of flecainide and tetracaine, a known RyR2 inhibitor ineffective in CPVT myocytes, on arrhythmogenic Ca2+ waves and elementary sarcoplasmic reticulum (SR) Ca2+ release events, Ca2+ sparks. In ventricular myocytes isolated from a CPVT mouse model, flecainide significantly reduced spark amplitude and spark width, resulting in a 40% reduction in spark mass. Surprisingly, flecainide significantly increased spark frequency. As a result, flecainide had no significant effect on spark-mediated SR Ca2+ leak or SR Ca2+... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189012 Thu, 15 Oct 2009 00:00:00 +0100 3189012 http://www.medworm.com/index.php?rid=3145792&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004295%2Fabstract%3Frss%3Dyes Abstract: We have developed a detailed mathematical model for Ca handling and ionic currents in the human ventricular myocyte. Our aims were to: (1) simulate basic excitation–contraction coupling phenomena; (2) use realistic repolarizing K current densities; (3) reach steady-state. The model relies on the framework of the rabbit myocyte model previously developed by our group, with subsarcolemmal and junctional compartments where ion channels sense higher [Ca] vs. bulk cytosol. Ion channels and transporters have been modeled on the basis of the most recent experimental data from human ventricular myocytes. Rapidly and slowly inactivating components of Ito have been formulated to differentiate between endocardial and epicardial myocytes. Transmural gradients of Ca handling proteins and Na... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145792 Thu, 15 Oct 2009 00:00:00 +0100 3145792 http://www.medworm.com/index.php?rid=2882893&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003940%2Fabstract%3Frss%3Dyes (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882893 Mon, 12 Oct 2009 15:14:54 +0100 2882893 http://www.medworm.com/index.php?rid=2882892&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228280900385X%2Fabstract%3Frss%3Dyes The publisher regrets that a production error resulted in the omission of the following conflict of interest statement. Ian Fearon has been employed within British American Tobacco Group R&D since March 2008 and is currently a stockholder in the company. Stephen Faux has been employed at Applied Technologies (Cambridge) Limited since June 2007 and within British American Tobacco Group R&D since April 2009, and is currently a stockholder in the company. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882892 Mon, 12 Oct 2009 15:14:54 +0100 2882892 http://www.medworm.com/index.php?rid=2882870&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003848%2Fabstract%3Frss%3Dyes It is a pleasure to congratulate Dr. Richard Bing on the occasion of his 100th birthday. A summary of his life and scientific contributions appears in this issue . It is fitting that this article appears in the Journal of Molecular and Cellular Cardiology as Dr. Bing (together with Lionel Opie) founded the journal in 1970 and was its first Editor in Chief. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882870 Mon, 12 Oct 2009 15:14:51 +0100 2882870 http://www.medworm.com/index.php?rid=2882869&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003885%2Fabstract%3Frss%3Dyes (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882869 Mon, 12 Oct 2009 15:14:51 +0100 2882869 http://www.medworm.com/index.php?rid=3258699&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004167%2Fabstract%3Frss%3Dyes Abstract: Matrix metalloproteinases (MMPs) are a group of proteases known to regulate the turnover of extracellular matrix and thus are suggested to be important in the process of several diseases associated with tissue remodeling. Furthermore, the concept that modulation of airway remodeling including excessive proteolysis damage of the tissue, may be of interest as a basis for future treatment. Degradation of extracellular matrix is currently associated with structural and recruited cell activation and release of inflammatory mediators and MMPs. Indeed, a marked increase in their expression is observed associated with a variety of inflammatory diseases, including respiratory pathologies. In these conditions, we have to consider MMPs as therapeutic targets which can be inhibited by non-se... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3258699 Fri, 09 Oct 2009 00:00:00 +0100 3258699 http://www.medworm.com/index.php?rid=3189021&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004155%2Fabstract%3Frss%3Dyes Abstract: Cardiac contraction is initiated by the release of Ca2+ from intracellular stores in response to an action potential, in a process known as “excitation–contraction coupling” (ECC). Here we investigate the maturation of ECC in the rat heart during postnatal development. We provide new information on how proteins of the sarcoplasmic reticulum (SR) and the t-tubules (TTs) assemble to form the structures that support EC coupling during postnatal development. We show that the surface membrane protein, caveolin-3 (Cav3), is a good protein marker for TTs in ventricular myocytes and compared it quantitatively to junctophilin-2 (JP2), a protein found on the SR at sites of SR-TT junctions, or couplons. Although JP2 and Cav3 associate primarily with the SR and TTs, respectively, we fo... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189021 Fri, 09 Oct 2009 00:00:00 +0100 3189021 http://www.medworm.com/index.php?rid=3258700&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228280900412X%2Fabstract%3Frss%3Dyes Abstract: Unraveling the biological role of tissue inhibitors of metalloproteinases (TIMPs) during cardiac remodeling and the progression of heart failure has proven to be an enormous challenge. Remodeling of the cardiac extracellular matrix (ECM), regulated by matrix metalloproteinases (MMPs) and their endogenous inhibitors, TIMPs, is a well-established paradigm in cardiac health and disease. Originally, TIMPs were thought to function exclusively as endogenous inhibitors of MMP activity, thereby fine-tuning MMP-mediated ECM degradation and numerous related processes. However, during the last two decades, the concept of MMP-independent TIMP-mediated receptor signaling and regulation of cell fate has emerged. Although our current knowledge is still limited, in this review, we highlight some... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3258700 Mon, 05 Oct 2009 00:00:00 +0100 3258700 http://www.medworm.com/index.php?rid=3189011&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004131%2Fabstract%3Frss%3Dyes Abstract: Two cardiomyopathic mutations were expressed in human cardiac actin, using a Baculovirus/insect cell system; E99K is associated with hypertrophic cardiomyopathy whereas R312H is associated with dilated cardiomyopathy. The hypothesis that the divergent phenotypes of these two cardiomyopathies are associated with fundamental differences in the molecular mechanics and thin filament regulation of the underlying actin mutation was tested using the in vitro motility and laser trap assays. In the presence of troponin (Tn) and tropomyosin (Tm), β-cardiac myosin moved both E99K and R312H thin filaments at significantly (p (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189011 Mon, 05 Oct 2009 00:00:00 +0100 3189011 http://www.medworm.com/index.php?rid=2967069&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004118%2Fabstract%3Frss%3Dyes Abstract: Although nitric oxide (NO) has received extensive attention as an anti-hypertrophic agent the mechanisms underlying its regulation of endothelin-1 (ET-1) have not been fully elucidated. Since RhoA has been identified as an important mediator of cardiac hypertrophy and is inhibited by NO in vascular tissue, we sought to determine whether the anti-ET-1 effects of NO in cardiomyocytes were mediated via inhibition of the RhoA-ROCK cascade in the context of cardiac hypertrophy. Neonatal rat ventricular myocytes were cultured in the presence of ET-1 (10 nM) with or without pre-treatment with the NO donor S-nitroso-n-acetylpenicillamine (SNAP; 100 μM), 8-Br-cGMP (cGMP; 100 μM), the RhoA inhibitor C3 exoenzyme (C3; 30 ng/ml), or the ROCK inhibitor Y-27632 (10 μM). ET-1-induced ca... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2967069 Mon, 05 Oct 2009 00:00:00 +0100 2967069 http://www.medworm.com/index.php?rid=2967064&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004143%2Fabstract%3Frss%3Dyes Abstract: The insulin receptor substrate (IRS) family plays important roles in cellular growth, signaling, and survival in the brain. We identified IRS6/Dok-5, a member of the IRS family, also expressed in heart. Dok-5 expression level significantly increased during cardiomyocyte differentiation of P19CL6 cells. To understand the mechanism of Dok-5 gene expression and regulation during cardiomyocyte differentiation, we first mapped the transcription start site of the mouse Dok-5 gene and characterized its promoter regions. Truncation and mutation analysis of the Dok-5 promoter identified the forkhead binding element responsible for the repression of Dok-5 promoter activation. The co-localization of FOXO3a and Dok-5 in the mouse heart allows FOXO3a to be a transcriptional regulator of Dok-5... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2967064 Mon, 05 Oct 2009 00:00:00 +0100 2967064 http://www.medworm.com/index.php?rid=2967062&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809004106%2Fabstract%3Frss%3Dyes Nitric oxide, generated by the nitric oxide synthase (NOS) enzymes, plays pivotal roles in cardiovascular homeostasis and in the pathogenesis of cardiovascular disease. The NOS cofactor, tetrahydrobiopterin (BH4), is an important regulator of NOS function, since BH4 is required to maintain enzymatic coupling of l-arginine oxidation, to produce NO. Loss or reduction of BH4 is associated with NOS uncoupling, resulting in production of superoxide rather than NO. Electron paramagnetic resonance spectroscopy studies have shown that BH4 both stabilizes and donates electrons to the ferrous-dioxygen complex in the oxygenase domain, as the initiating step of l-arginine oxidation. In this reaction BH4 forms the protonated trihydrobiopterin cation radical, and is then reduced by electron transfer fro... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2967062 Mon, 05 Oct 2009 00:00:00 +0100 2967062 http://www.medworm.com/index.php?rid=2967066&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003812%2Fabstract%3Frss%3Dyes This study evaluates whether carbamylated erythropoietin is as effective as recombinant human erythropoietin in protecting endothelial progenitor cells (EPCs) from apoptosis without stimulating erythropoiesis. Experiments were performed in an erythroid cell line (UT-7) and in human EPCs. Cell signals regulating proliferation and apoptosis (Jak-2, Akt, Erk1/2, NFκB and Stat-5) were measured by Western blotting. In human EPCs, cell senescence, apoptosis and proliferation were assessed by acidic β-gal and measurement of telomere length, TUNEL and PCNA labeling, respectively. Angiogenesis was evaluated using the endothelial tube formation assay. In UT-7, carbamylated erythropoietin (C-darbe) induced phosphorylation of the anti-apoptotic Jak-2/Akt signal and, as opposed to recombinant human e... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2967066 Fri, 25 Sep 2009 00:00:00 +0100 2967066 http://www.medworm.com/index.php?rid=3258697&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003836%2Fabstract%3Frss%3Dyes For many years, analyses of the heart have focused primarily on the role of the myocytes as the principal cell type that generates force. Analyses of the extracellular matrix (ECM) were deemed important, but primarily relevant only in hypertrophy and after myocardial infarction. Related to the ECM was the role of the fibroblast, the principal cell type that makes the ECM. When analyses of the ECM were performed, the focus was primarily on interstitial collagen. This reductionist approach was also incorporated into the experimental design of in vitro studies that used planar two-dimensional culture systems. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3258697 Thu, 24 Sep 2009 00:00:00 +0100 3258697 http://www.medworm.com/index.php?rid=3189014&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003800%2Fabstract%3Frss%3Dyes Abstract: While compelling evidence supports the central role of mitochondrial dysfunction in the pathogenesis of heart failure, there is comparatively less information available on mitochondrial alterations that occur prior to failure. Building on our recent work with the dystrophin-deficient mdx mouse heart, this review focuses on how early changes in mitochondrial functional phenotype occur prior to overt cardiomyopathy and may be a determinant for the development of adverse cardiac remodelling leading to failure. These include alterations in energy substrate utilization and signalling of cell death through increased permeability of mitochondrial membranes, which may result from abnormal calcium handling, and production of reactive oxygen species. Furthermore, we will discuss evidence s... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3189014 Tue, 22 Sep 2009 00:00:00 +0100 3189014 http://www.medworm.com/index.php?rid=2967068&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003824%2Fabstract%3Frss%3Dyes We examined the possibility that ATRAP could attenuate AT1 receptor-mediated vascular senescence via inactivation with the calcineurin/NFAT pathway. Ang II stimulation significantly increased senescence-associated β-galactosidase (SA-β-gal)-stained cells, oxidative stress, and expression of p53 and p21 in wild-type (WT) vascular smooth muscle cells (VSMC). Moreover, in WT VSMC, Ang II stimulation enhanced NFAT transcriptional activity, which was prevented by CAML-siRNA treatment. NFAT-siRNA treatment attenuated Ang-II-increased SA-β-gal activity and p53 and p21 expression. Treatment with a calcineurin activity inhibitor, cyclosporin A, reduced Ang-II-induced NFAT transcriptional activity and senescent VSMC. In contrast, VSMC prepared from ATRAP transgenic (ATRAP-Tg) mice exhibited atten... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2967068 Tue, 22 Sep 2009 00:00:00 +0100 2967068 http://www.medworm.com/index.php?rid=2882873&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002326%2Fabstract%3Frss%3Dyes In this study, we tested whether lack of β3-AR influences the myocardial response to pressure-overload. Baseline echocardiography in mice lacking β3-AR (β3−/−) compared to wild type (WT) showed mild LV hypertrophy at 8 weeks that worsened as they aged. β3−/− mice had much greater mortality after transverse aortic constriction (TAC) than WT controls. By 3 weeks of TAC, systolic function was worse. After 9 weeks of TAC, β3−/− mice also had greater LV dilation, myocyte hypertrophy and enhanced fibrosis. NOS activity declined in β3−/−TAC hearts after 9 weeks, and total and NOS-dependent superoxide rose, indicating heightened oxidative stress and NOS uncoupling. The level of eNOS phosphorylation in β3−/−TAC hearts was diminished, and nNOS and iNOS expression level... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882873 Mon, 21 Sep 2009 23:00:00 +0100 2882873 http://www.medworm.com/index.php?rid=3258702&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003770%2Fabstract%3Frss%3Dyes Abstract: Atrial fibrosis has been strongly associated with the presence of heart diseases/arrhythmias, including congestive heart failure (CHF) and atrial fibrillation (AF). Inducibility of AF as a result of atrial fibrosis has been the subject of intense recent investigation since it is the most commonly encountered arrhythmia in adults and can substantially increase the risk of premature death. Rhythm and rate control drugs as well as surgical interventions are used as therapies for AF; however, increased attention has been diverted to mineralocorticoid receptor (MR) antagonists including spironolactone as potential therapies for human AF because of their positive effects on reducing atrial fibrosis and associated AF in animal models. Spironolactone has been shown to exert positive effe... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3258702 Mon, 14 Sep 2009 00:00:00 +0100 3258702 http://www.medworm.com/index.php?rid=3258701&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003782%2Fabstract%3Frss%3Dyes Abstract: This review addresses new concepts related to the importance of how cells within the cardiovascular system respond to matricryptic sites generated from the extracellular matrix (ECM) following tissue injury. A model is presented whereby matricryptic sites exposed from the ECM result in activation of multiple cell surface receptors including integrins, scavenger receptors, and toll-like receptors which together are hypothesized to coactivate downstream signaling pathways which alter cell behaviors following tissue injury. Of great interest are the relationships between matricryptic fragments of ECM called matricryptins and other stimuli that activate cells during injury states such as released components from cells (DNA, RNA, cytoskeletal components such as actin) or products from... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3258701 Mon, 14 Sep 2009 00:00:00 +0100 3258701 http://www.medworm.com/index.php?rid=2967067&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003794%2Fabstract%3Frss%3Dyes Abstract: During cardiac arrest (CA), myocardial perfusion is solely dependent on cardiopulmonary resuscitation (CPR) although closed-chest compressions only provide about 10–20% of normal myocardial perfusion. The study was conducted in a whole animal CPR model to determine whether CPR-generated oxygen delivery preserves or worsens mitochondrial function. Male Sprague-Dawley rats (400–450 g) were randomly divided into four groups: (1) BL (instrumentation only, no cardiac arrest), (2) CA15 (15 min cardiac arrest without CPR), (3) CA25 (25 min cardiac arrest without CPR) and (4) CPR (15 min cardiac arrest, followed by 10 min CPR). The differences between groups were evaluated by measuring mitochondrial respiration, electron transport chain (ETC) complex activities and mitochondrial... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2967067 Mon, 14 Sep 2009 00:00:00 +0100 2967067 http://www.medworm.com/index.php?rid=3145797&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228280900368X%2Fabstract%3Frss%3Dyes Abstract: The zebrafish has recently emerged as an excellent model for studies of heart development and regeneration. The physiology of the zebrafish heart has been suggested to resemble that of the human heart in many aspects, whereas, in contrast to mammals, the zebrafish has a remarkable ability to regenerate after heart injury. Thus, zebrafish have been proposed as a cost-effective model for genetic and pharmacological screens of factors affecting heart function and repair. However, realizing the full potential of the zebrafish heart as a model will require a better understanding of the electrophysiology of the adult zebrafish myocardium. Here, we characterize action potentials (APs) from intact adult atria and ventricles and find that the overall shape of zebrafish APs is similar to t... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145797 Thu, 10 Sep 2009 00:00:00 +0100 3145797 http://www.medworm.com/index.php?rid=3145796&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003691%2Fabstract%3Frss%3Dyes Abstract: Classically, cardiac sarcolemmal KATP channels have been thought to be composed of Kir6.2 (KCNJ11) and SUR2A (ABCC9) subunits. However, the evidence is strong that SUR1 (sulfonylurea receptor type 1, ABCC8) subunits are also expressed in the heart and that they play a significant functional role in the atria. To examine this further, we have assessed the effects of isotype-specific potassium channel-opening drugs, diazoxide (specific to SUR1>SUR2A) and pinacidil (SUR2A>SUR1), in intact hearts from wild-type mice (WT, n=6), SUR1−/− (n=6), and Kir6.2−/− mice (n=5). Action potential durations (APDs) in both atria and ventricles were estimated by optical mapping of the posterior surface of Langendorff-perfused hearts. To confirm the atrial effect of both openers, isolated atr... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145796 Wed, 09 Sep 2009 00:00:00 +0100 3145796 http://www.medworm.com/index.php?rid=3145795&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003708%2Fabstract%3Frss%3Dyes Abstract: The transient outward potassium current (Ito) in cardiac myocytes is mainly mediated by members of the Kv4 subfamily of voltage-gated potassium channels. Several in vitro studies have shown that angiotensin II (Ang II), which plays an important role in the development of cardiac hypertrophy, rapidly downregulates Kv4.3 mRNA expression. However, it is not clear whether Ang II regulates Ito in vivo and whether this regulation may depend on alterations in Kv4.3 gene expression. To address this question, we determined the effects of acute (24 h) and chronic (14 days) exogenous infusions of Ang II on Ito and the expression of its channel subunits in the mouse left ventricle. Ang II rapidly increased blood pressure and reduced Kv4.2 but not Kv4.3 mRNA levels in the absence of cardiac ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145795 Wed, 09 Sep 2009 00:00:00 +0100 3145795 http://www.medworm.com/index.php?rid=3145794&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003757%2Fabstract%3Frss%3Dyes Abstract: Lysophosphatidylcholine (LPC) accumulation in intracellular and/or interstitial space in cardiomyocytes may underlie as a mechanism for tachycardia and various arrhythmias during cardiac ischemia, which is usually accompanied by elevation of intracellular Ca2+ concentration ([Ca2+]i). The present study was therefore designed to investigate possible mechanisms responsible for [Ca2+]i elevation by LPC focusing on T-type Ca2+ channel current (ICa.T). LPC as well as phorbol 12-myristate 13-acetate (PMA) significantly accelerated the beating rates of neonatal rat cardiomyocytes. Augmentation of ICa.T by LPC was dependent on the intracellular Ca2+ concentration: an increase of ICa.T was significantly larger in high [Ca2+]i condition (pCa=7) than those in low [Ca2+]i condition (pCa=11).... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145794 Wed, 09 Sep 2009 00:00:00 +0100 3145794 http://www.medworm.com/index.php?rid=3145793&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003769%2Fabstract%3Frss%3Dyes In conclusion, β-adrenergic receptor stimulation exaggerates BVR during IKs blockade, indicating a BVR-stabilizing role of β-adrenergic-sensitive IKs. Loss of IKs plus overriding of Ca2+-dependent membrane currents, including inward Na+–Ca2+ exchange current, conspire to proarrhythmic BVR under these conditions. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145793 Wed, 09 Sep 2009 00:00:00 +0100 3145793 http://www.medworm.com/index.php?rid=3145789&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003721%2Fabstract%3Frss%3Dyes Abstract: The electrical properties of the atria and ventricles differ in several aspects reflecting the distinct role of the atria in cardiac physiology. The study of atrial electrophysiology had greatly contributed to the understanding of the mechanisms of atrial fibrillation (AF). Only the atrial L-type calcium current is regulated by serotonine or, under basal condition, by phosphodiesterases. These distinct regulations can contribute to ICa down-regulation observed during AF, which is an important determinant of action potential refractory period shortening. The voltage-gated potassium current, IKur, has a prominent role in the repolarization of the atrial but not ventricular AP. In many species, this current is based on the functional expression of KV1.5 channels, which might represe... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145789 Wed, 09 Sep 2009 00:00:00 +0100 3145789 http://www.medworm.com/index.php?rid=3145779&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003678%2Fabstract%3Frss%3Dyes Abstract: The cardiac voltage-gated Na+ channel Nav1.5 generates the cardiac Na+ current (INa). Mutations in SCN5A, the gene encoding Nav1.5, have been linked to many cardiac phenotypes, including the congenital and acquired long QT syndrome, Brugada syndrome, conduction slowing, sick sinus syndrome, atrial fibrillation, and dilated cardiomyopathy. The mutations in SCN5A define a sub-group of Nav1.5/SCN5A-related phenotypes among cardiac genetic channelopathies. Several research groups have proposed that Nav1.5 may be part of multi-protein complexes composed of Nav1.5-interacting proteins which regulate channel expression and function. The genes encoding these regulatory proteins have also been found to be mutated in patients with inherited forms of cardiac arrhythmias. The proteins that a... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145779 Wed, 09 Sep 2009 00:00:00 +0100 3145779 http://www.medworm.com/index.php?rid=2882882&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228280900371X%2Fabstract%3Frss%3Dyes Abstract: Insulin-like growth factor-1 (IGF-1) signaling has recently been implicated in the development of cardiac hypertrophy after long-term endurance training, via mechanisms that may involve energetic stress. Given the potential overlap of insulin and IGF-1 signaling we sought to determine if both signaling pathways could contribute to exercise-induced cardiac hypertrophy following shorter-term exercise training. Studies were performed in mice with cardiac-specific IGF-1 receptor (IGF1R) knockout (CIGFRKO), mice with cardiac-specific insulin receptor (IR) knockout (CIRKO), CIGFRKO mice that lacked one IR allele in cardiomyocytes (IGFR−/−IR+/−), and CIRKO mice that lacked one IGF1R allele in cardiomyocytes (IGFR+/−IR−/−). Intravenous administration of IGF-1 or 75 hours of ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882882 Tue, 08 Sep 2009 23:00:00 +0100 2882882 http://www.medworm.com/index.php?rid=2882877&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003745%2Fabstract%3Frss%3Dyes In this study we determine whether the metabolic coupling to function improves with SERCA treatment. PBS (control) or adenovirus carrying the cDNA for SERCA1 was delivered via coronary perfusion in vivo to Sprague-Dawley rat hearts. Three days following gene transfer, isolated hearts were perfused with 0.4 mM [2,4,6,8,10,12,14,16-13C8] palmitate and 5 mM glucose, and subjected to 15-min ischemia followed by 40-min reperfusion. Consistent with myocardial stunning, rate pressure product (RPP) and left ventricular developed pressure (LVDP) were depressed 30–40% (p (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882877 Tue, 08 Sep 2009 23:00:00 +0100 2882877 http://www.medworm.com/index.php?rid=2882874&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003733%2Fabstract%3Frss%3Dyes Abstract: Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that controls inflammatory processes, and inflammation is known to play an important role in the pathogenesis of atrial fibrillation (AF). The present study sought to investigate whether MIF expression is responsible for the changes in L-type Ca2+ currents (ICa,L) seen in AF. Whole-cell voltage-clamp recordings and biochemical assays were used to study the regulation and expression of ICa,L in human atrial myocytes and in HL-1 cells. Basal ICa,L was reduced in AF compared to sinus rhythm (SR) controls, mRNA and protein levels of the pore-forming α1C subunit of L-type Ca2+ channel (LCC α1C) were also decreased, while MIF expression levels were increased in AF. Levels of Src and activated Src (p-Src Y416) were... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882874 Tue, 08 Sep 2009 23:00:00 +0100 2882874 http://www.medworm.com/index.php?rid=2761682&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003423%2Fabstract%3Frss%3Dyes (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2761682 Thu, 03 Sep 2009 18:08:32 +0100 2761682 http://www.medworm.com/index.php?rid=3350146&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003629%2Fabstract%3Frss%3Dyes Abstract: During ageing, the function of sinoatrial node (SAN), the pacemaker of the heart, declines, and the incidence of sick sinus syndrome increases markedly. The aim of the study was to investigate structural and functional remodelling of the SAN during ageing. Rats, 3 and 24 months old (equivalent to young adult and ∼69-year-old humans), were studied. Extracellular potential recording from right atrial preparations showed that (as expected) the intrinsic heart rate was slower in the old animals. It also showed a shift of the leading pacemaker site towards the inferior vena cava in the old animals. Consistent with this, intracellular potential recording showed that slow pacemaker action potentials were more widespread and extended further towards the inferior vena cava in old animal... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350146 Wed, 02 Sep 2009 00:00:00 +0100 3350146 http://www.medworm.com/index.php?rid=3258704&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003605%2Fabstract%3Frss%3Dyes Abstract: The extracellular matrix is not only a scaffold that provides support for cells, but it is also involved in cell–cell interactions, proliferation and migration. The intricate relationships among the cellular and acellular components of the heart drive proper heart development, homeostasis and recovery following pathological injury. Cardiac myocytes, fibroblasts and endothelial cells differentially express and respond to particular extracellular matrix factors that contribute to cell communication and overall cardiac function. In addition, turnover and synthesis of ECM components play an important role in cardiac function. Therefore, a better understanding of these factors and their regulation would lend insight into cardiac development and pathology, and would open doors to nov... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3258704 Wed, 02 Sep 2009 00:00:00 +0100 3258704 http://www.medworm.com/index.php?rid=3258703&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003666%2Fabstract%3Frss%3Dyes Abstract: Myocarditis is an inflammatory disorder induced most commonly by infectious agents. The natural course of the disease is broad and ranges from complete recovery to dilated cardiomyopathy and death. The mechanisms of the incomplete recovery remain poorly understood but extracellular matrix remodelling by metalloproteinases seems to be important for the progression to dilated cardiomyopathy and chronic heart failure. The matrix metalloproteinases (MMPs) are proteolytic enzymes whose role was thought to be the degradation of matrix components only. In the last few years a considerable amount of evidence has gathered which shows new functions of the MMPs as powerful modulatory factors in inflammatory disorders. MMPs facilitate the migration of immune cells through the basement membra... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3258703 Wed, 02 Sep 2009 00:00:00 +0100 3258703 http://www.medworm.com/index.php?rid=3145787&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003642%2Fabstract%3Frss%3Dyes Abstract: Gap junctions form the intercellular pathway for cell-to-cell transmission of the cardiac impulse from its site of origin, the sinoatrial node, along the atria, the atrioventricular conduction system to the ventricular myocardium. The component parts of gap junctions are proteins called connexins (Cx), of which three main isoforms are found in the conductive and working myocardial cells: Cx40, Cx43, and Cx45. These isoforms are regionally expressed in the heart, which suggests a specific role or function of a specific connexin in a certain part of the heart. Using genetically modified mice, the function of these connexins in the different parts of the heart have been assessed in the past years. This review will follow the cardiac impulse on its path through the heart and recapitu... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145787 Wed, 02 Sep 2009 00:00:00 +0100 3145787 http://www.medworm.com/index.php?rid=3145785&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003630%2Fabstract%3Frss%3Dyes Abstract: Two different Ca2+ channels exist in cardiac myocytes. While the L-type Ca2+ channel is ubiquitous and the main source of Ca2+ for excitation–contraction coupling and pacemaker activity, the functional role of the T-type Ca2+ channel is diverse and depends on mammalian species, heart region, age and various cardiac diseases. Two isoforms of T-type Ca2+ channel proteins in the heart, CaV3.1 and CaV3.2, are functionally expressed in embryonic hearts, but markedly diminish during development. In the adult heart, the T-type Ca2+ channel is almost undetectable in ventricular myocytes and is most prevalent in the conduction system, playing a functional role in facilitating pacemaker depolarization of the sinoatrial node. Interestingly, the T-type Ca2+ channel is re-expressed in atria... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145785 Wed, 02 Sep 2009 00:00:00 +0100 3145785 http://www.medworm.com/index.php?rid=2967065&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003654%2Fabstract%3Frss%3Dyes Abstract: Recently, we reported that histone deacetylase (HDAC) inhibitors block cardiac hypertrophy and that activation of HDAC2, one of the class I HDACs, is required for hypertrophy. In the present study, we tried to find the downstream target of HDAC inhibitor by utilizing cardiomyocytes and H9c2 cells. Both trichostatin A (TSA, class I and II HDAC inhibitor) and SK7041 (SK, class I HDAC blocker) attenuated the expression level and promoter activity of Nppa (natriuretic polypeptide precursor type A) and Myh7 (myosin heavy polypeptide 7), which are fetal genes associated with hypertrophy. Promoter-mapping revealed that the Nppa promoter region from −130 to approximately −105, which contains binding sites for Krüppel-like factor 4 (KLF4), is responsible for the HDAC inhibitor-mediat... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2967065 Wed, 02 Sep 2009 00:00:00 +0100 2967065 http://www.medworm.com/index.php?rid=2882883&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003617%2Fabstract%3Frss%3Dyes We examined PLC activation in right and left atrial appendage from patients with mitral valve disease (VHD) and in a mouse model of dilated cardiomyopathy caused by transgenic overexpression of the stress-activated protein kinase, mammalian sterile 20 like kinase 1 (Mst1) (Mst1-TG). PLC activation was heightened 6- to 10-fold in atria from VHD patients compared with right atrial tissue from patients undergoing coronary artery bypass surgery (CABG) and was also heightened in the dilated atria from Mst1-TG. PLC activation in human left atrial appendage and in mouse left atria correlated with left atrial size, implying a relationship between PLC activation and chronic dilatation. Dilated atria from human and mouse showed heightened expression of PLCβ1b, but not of other PLC subtypes. PLCβ1b... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882883 Tue, 01 Sep 2009 23:00:00 +0100 2882883 http://www.medworm.com/index.php?rid=2967072&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003307%2Fabstract%3Frss%3Dyes Abstract: Myocardial infarction (MI) leading to myocardial cell loss represents one of the common causes leading to cardiac failure. We have previously demonstrated the beneficial effects of several potent soluble epoxide hydrolase (sEH) inhibitors in cardiac hypertrophy. sEH catalizes the conversion of epoxyeicosatrienoic acids (EETs) to form the corresponding dihydroxyeicosatrienoic acids (DHETs). EETs are products of cytochrome P450 epoxygenases that have vasodilatory properties. Additionally, EETs inhibit the activation of nuclear factor (NF)-κB-mediated gene transcription. Motivated by the potential to uncover a new class of therapeutic agents for cardiovascular diseases which can be effectively used in clinical setting, we directly tested the biological effects of sEH inhibitors (sE... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2967072 Tue, 01 Sep 2009 00:00:00 +0100 2967072 http://www.medworm.com/index.php?rid=2882879&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003393%2Fabstract%3Frss%3Dyes Abstract: Most of the available evidence on the role of neutrophils on pathological cardiac remodeling has been pertained after acute myocardial infarction. However, whether neutrophils directly contribute to the pathogenesis of cardiac remodeling after events other than acute myocardial infarction remains unknown. Here we show that acute eccentric hypertrophy induced by aorto-caval fistula (ACF) in the rats induced an increase in the inflammatory response characterized by activation of the STAT pathway and increased infiltration of neutrophils in the myocardium. This early inflammation was associated with a decrease in interstitial collagen accumulation and an increase in myocyte apoptosis. Neutrophil infiltration blockade attenuated MMP activation, ECM degradation, and myocyte apoptosis ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882879 Mon, 31 Aug 2009 23:00:00 +0100 2882879 http://www.medworm.com/index.php?rid=3145783&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003368%2Fabstract%3Frss%3Dyes Abstract: Cardiac IK1 and IKACh are the major potassium currents displaying classical strong inward rectification, a unique property that is critical for their roles in cardiac excitability. In the last 15 years, research on IK1 and IKACh has been propelled by the cloning of the underlying inwardly rectifying potassium (Kir) channels, the discovery of the molecular mechanism of strong rectification and the linking of a number of disorders of cardiac excitability to defects in genes encoding Kir channels. Disease-causing mutations in Kir genes have been shown experimentally to affect one or more of the following channel properties: structure, assembly, trafficking, and regulation, with the ultimate effect of a gain- or a loss-of-function of the channel. It is now established that IK1 and I... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145783 Tue, 25 Aug 2009 00:00:00 +0100 3145783 http://www.medworm.com/index.php?rid=2967070&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228280900337X%2Fabstract%3Frss%3Dyes In conclusion, dietary supplementation with EPA + DHA altered mitochondrial membrane phospholipid fatty acid composition in normal and infarcted hearts, but delayed MPTP opening only in normal hearts. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2967070 Tue, 25 Aug 2009 00:00:00 +0100 2967070 http://www.medworm.com/index.php?rid=2882880&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003320%2Fabstract%3Frss%3Dyes Abstract: Class A scavenger receptor (SR-A) plays an important role in foam cell formation. However, the mechanism underlying the internalization of the receptor–ligand complexes remains unclear. The aim of the present study was to investigate the molecular mechanism to regulate SR-A-mediated intracellular lipid accumulation in macrophages. A pull-down assay was performed and glucose-regulated protein 78 (GRP78) was identified to bind with the cytoplasmic domain of SR-A (CSR-A). Immunoprecipitation and artificially expressed protein binding assay demonstrated the direct specific binding of GRP78 with SR-A in cells. Indirect immunofluorescence assay and western blot analysis showed their co-localization in membrane and cytoplasm. Over-expression of GRP78 specifically inhibited SR-A-mediat... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882880 Thu, 20 Aug 2009 23:00:00 +0100 2882880 http://www.medworm.com/index.php?rid=3350159&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003277%2Fabstract%3Frss%3Dyes In conclusion, heat stress responses change calcium handling through protein but not RNA regulation. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350159 Wed, 19 Aug 2009 00:00:00 +0100 3350159 http://www.medworm.com/index.php?rid=2967071&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003290%2Fabstract%3Frss%3Dyes In this study, we examined the mechanism by which NOTCH1 represses aortic valve calcification. Heterozygous Notch1-null (Notch1+/-) mice had greater than fivefold more aortic valve calcification than age- and sex-matched wildtype littermates. Inhibition of Notch signaling in cultured sheep aortic valve interstitial cells (AVICs) also increased calcification more than fivefold and resulted in gene expression typical of osteoblasts. We found that Notch1 normally represses the gene encoding bone morphogenic protein 2 (Bmp2) in murine aortic valves in vivo and in aortic valve cells in vitro. siRNA-mediated knockdown of Bmp2 blocked the calcification induced by Notch inhibition in AVICs. These findings suggest that Notch1 signaling in aortic valve cells represses osteoblast-like calcification p... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2967071 Wed, 19 Aug 2009 00:00:00 +0100 2967071 http://www.medworm.com/index.php?rid=2882890&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003344%2Fabstract%3Frss%3Dyes Abstract: Extracellular superoxide dismutase (EC-SOD) is an antioxidant that protects the heart from ischemia and the lung from inflammation and fibrosis. The role of cardiac EC-SOD under normal conditions and injury remains unclear. Cardiac toxicity, a common side effect of doxorubicin, involves oxidative stress. We hypothesize that EC-SOD is critical for normal cardiac function and protects the heart from oxidant-induced fibrosis and loss of function. C57BL/6 and EC-SOD-null mice were treated with doxorubicin, 15 mg/kg (i.p.). After 15 days, echocardiography was used to assess cardiac function. Left ventricle (LV) tissue was used to assess fibrosis and inflammation by staining, Western blot, and hydroxyproline analysis. At baseline, EC-SOD-null mice have LV wall thinning and increases ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882890 Tue, 18 Aug 2009 23:00:00 +0100 2882890 http://www.medworm.com/index.php?rid=2882884&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003332%2Fabstract%3Frss%3Dyes In conclusion, A2A and A2B receptors work in concert to prevent reperfusion injury in rat hearts treated with NECA. NECA may protect the heart by modulating the mPTP opening through inactivating mitochondrial GSK-3β. A simultaneous stimulation of A2A and A2B receptors at reperfusion is required to produce a strong cardioprotection against reperfusion injury. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882884 Tue, 18 Aug 2009 23:00:00 +0100 2882884 http://www.medworm.com/index.php?rid=2882871&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003289%2Fabstract%3Frss%3Dyes The upcoming 100th birthday of Dr. Richard J. Bing () provides a welcome opportunity to reflect on this extraordinary man, on the times he has lived in, and on the contributions he has made to investigative cardiology, spanning nearly seven decades of original work. In addition we celebrate in Dr. Bing as one of the founders of the International Study Group for Research in Cardiac Metabolism, later renamed International Society for Heart Research (ISHR) and a founding editor of this Journal. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882871 Tue, 18 Aug 2009 23:00:00 +0100 2882871 http://www.medworm.com/index.php?rid=3258706&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003253%2Fabstract%3Frss%3Dyes Abstract: Extracellular matrix (ECM) components play essential roles in development, remodeling, and signaling in the cardiovascular system. They are also important in determining the mechanics of blood vessels, valves, pericardium, and myocardium. The goal of this brief review is to summarize available information regarding the mechanical contributions of ECM in the myocardium. Fibrillar collagen, elastin, and proteoglycans all play crucial mechanical roles in many tissues in the body generally and in the cardiovascular system specifically. The myocardium contains all three components, but their mechanical contributions are relatively poorly understood. Most studies of ECM contributions to myocardial mechanics have focused on collagen, but quantitative prediction of mechanical properties ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3258706 Mon, 17 Aug 2009 00:00:00 +0100 3258706 http://www.medworm.com/index.php?rid=3145782&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003319%2Fabstract%3Frss%3Dyes Abstract: The two components of the cardiac delayed rectifier current have been the subject of numerous studies since firstly described. This current controls the action potential duration and is highly regulated. After identification of the channel subunits underlying IKs, KCNQ1 associated with KCNE1, and IKr, HERG, their involvement in human cardiac channelopathies have provided various models allowing the description of the molecular mechanisms of the KCNQ1 and HERG channels trafficking, activity and regulation. More recently, studies have been focusing on the unveiling of different partners of the pore-forming proteins that contribute to their maturation, trafficking, activity and/or degradation, on one side, and on their respective expression in the heterogeneous cardiac tissue, on th... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145782 Mon, 17 Aug 2009 00:00:00 +0100 3145782 http://www.medworm.com/index.php?rid=2882876&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003228%2Fabstract%3Frss%3Dyes Abstract: Cell transplantation improves cardiac function after myocardial infarction; however, the underlying mechanisms are not well-understood. Therefore, the goals of this study were to determine if neonatal rat cardiomyocytes transplanted into adult rat hearts 1 week after infarction would, after 8–10 weeks: 1) improve global myocardial function, 2) contract in a Ca2+ dependent manner, 3) influence mechanical properties of remote uninjured myocardium and 4) alter passive mechanical properties of infarct regions. The cardiomyocytes formed small grafts of ultrastructurally maturing myocardium that enhanced fractional shortening compared to non-treated infarcted hearts. Chemically demembranated tissue strips of cardiomyocyte grafts produced force when activated by Ca2+, whereas scar tis... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882876 Sun, 16 Aug 2009 23:00:00 +0100 2882876 http://www.medworm.com/index.php?rid=2882872&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228280900323X%2Fabstract%3Frss%3Dyes Abstract: Adipose tissue-derived stem cells have been demonstrated to differentiate into cardiomyocytes and vascular endothelial cells. Here we investigate whether mature adipocyte-derived dedifferentiated fat (DFAT) cells can differentiate to cardiomyocytes in vitro and in vivo by establishing DFAT cell lines via ceiling culture of mature adipocytes. DFAT cells were obtained by dedifferentiation of mature adipocytes from GFP-transgenic rats. We evaluated the differentiating ability of DFAT cells into cardiomyocytes by detection of the cardiac phenotype markers in immunocytochemical and RT-PCR analyses in vitro. We also examined effects of the transplantation of DFAT cells into the infarcted heart of rats on cardiomyocytes regeneration and angiogenesis. DFAT cells expressed cardiac phenoty... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882872 Sun, 16 Aug 2009 23:00:00 +0100 2882872 http://www.medworm.com/index.php?rid=2761698&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003101%2Fabstract%3Frss%3Dyes In conclusion, our results demonstrate that Na,K-β1 plays an essential role in regulating cardiac contractility and that its loss is associated with significant pathophysiology of the heart. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2761698 Sun, 16 Aug 2009 23:00:00 +0100 2761698 http://www.medworm.com/index.php?rid=3258705&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003265%2Fabstract%3Frss%3Dyes Abstract: The circulating renin-angiotensin system (RAS) is a classic endocrine system that regulates cardiovascular homeostasis during physiologic and pathologic states. Accumulated evidence has shown the presence of components of RAS in various tissues, which are upregulated in certain pathological conditions. Locally produced angiotensin (Ang)II may play an important role in tissue repair/remodeling in autocrine and/or paracrine manners. Following acute myocardial infarction (MI), cardiac repair occurs in the infarcted myocardium and structural remodeling is developed in noninfarcted myocardium, which are accompanied by activated cardiac RAS. In this review, the current understanding of independent activation of cardiac RAS and its regulation in the pathogenesis of myocardial repair/rem... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3258705 Thu, 13 Aug 2009 00:00:00 +0100 3258705 http://www.medworm.com/index.php?rid=2882878&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003241%2Fabstract%3Frss%3Dyes In conclusion, extracellular ATP activates purinergic receptors and induces arrhythmic activity through modifications of Ca2+ homeostasis and an activation of depolarizing membrane currents. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882878 Tue, 11 Aug 2009 23:00:00 +0100 2882878 http://www.medworm.com/index.php?rid=3350160&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003198%2Fabstract%3Frss%3Dyes This study provides the first evidence that inhibition of CCL5/RANTES exerts cardioprotective effects during early myocardial reperfusion, through its anti-inflammatory properties. Our findings indicate that blocking chemokine receptor/ligand interactions might become a novel therapeutic strategy to reduce reperfusion injuries in patients during acute coronary syndromes. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3350160 Mon, 10 Aug 2009 00:00:00 +0100 3350160 http://www.medworm.com/index.php?rid=3145798&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003204%2Fabstract%3Frss%3Dyes Abstract: In rabbit, sodium current (INa) contributes to newborn sinoatrial node (SAN) automaticity but is absent in adult SAN, where heart rate is slower. In contrast, heart rate is high and INa is functional in adult mouse SAN. Given the slower heart rates of large mammals, we asked if INa is functionally active in SAN of newborn or adult canine heart. SAN cells were isolated from newborn (6–10 days), young (40–43 days) and adult mongrels. INa was observed in >80% of cells from each age. However, current density was markedly greater in newborn, decreasing with age. At all ages, INa was sensitive to nanomolar tetrodotoxin (TTX); 100 nmol/L inhibited INa by 46.7%, 59.9% and 90.7% in newborn, young and adult cells, respectively. While high TTX sensitivity suggested the presence of no... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145798 Mon, 10 Aug 2009 00:00:00 +0100 3145798 http://www.medworm.com/index.php?rid=3145791&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003216%2Fabstract%3Frss%3Dyes Abstract: Although the action potential (AP) can be considered an “old acquaintance” by now, the complexity of the mutual interplay between membrane potential course and the underlying currents can still hold secrets, whose revelation may help in the interpretation of otherwise puzzling observations. The aim of this brief review is to analyze such an interplay from two viewpoints: how membrane current sets membrane potential course and how membrane potential course may, in turn, affect individual channel activity. The outcome of this analysis leads to the general conclusion that considering the “dynamic” nature of membrane potential is of major importance in explaining the physiological and pharmacological modulation of the AP. To illustrate this conclusion, specific issues are dis... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145791 Mon, 10 Aug 2009 00:00:00 +0100 3145791 http://www.medworm.com/index.php?rid=3145781&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003186%2Fabstract%3Frss%3Dyes Abstract: L-type Ca2+ channels are mediators of Ca2+ influx and the regulatory events accompanying it and are pivotal in the function and dysfunction of ventricular cardiac myocytes. L-type Ca2+ channels are located in sarcolemma, including the T-tubules facing the sarcoplasmic reticulum junction, and are activated by membrane depolarization, but intracellular Ca2+-dependent inactivation limits Ca2+ influx during action potential. ICaL is important in heart function because it triggers excitation–contraction coupling, modulates action potential shape and is involved in cardiac arrhythmia. L-type Ca2+ channels are multi-subunit complexes that interact with several molecules involved in their regulations, notably by β-adrenergic signaling. The present review highlights some of the recent ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145781 Wed, 05 Aug 2009 00:00:00 +0100 3145781 http://www.medworm.com/index.php?rid=2967063&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003174%2Fabstract%3Frss%3Dyes Abstract: Folate supplementation improves endothelial function in patients with hyperhomocysteinemia. Mechanistic insights into potential benefits of folate on vascular function in general population however, remain mysterious. Expression of dihydrofolate reductase (DHFR) was markedly increased by folic acid (FA, 50 μmol/L, 24 h) treatment in endothelial cells. Tetrahydrofolate (THF) is formed after incubation of purified DHFR or cellular extracts with 50 μmol/L of substrate dihydrofolic acid. THF could then be detected and quantified by high performance liquid chromatography (HPLC) with a fluorescent detector (295/365 nm). Using this novel and sensitive assay, we found that DHFR activity was significantly increased by FA. Furthermore, FA improved redox status of Ang II treated cells... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2967063 Wed, 05 Aug 2009 00:00:00 +0100 2967063 http://www.medworm.com/index.php?rid=2882886&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003162%2Fabstract%3Frss%3Dyes Abstract: Doxorubicin is known to have cumulative dose-dependent cardiotoxicity, and a tumor suppressor protein p53 has been implicated in the pathogenesis of doxorubicin cardiotoxicity. However, how p53 is induced by doxorubicin and mediates the cardiotoxic effects of doxorubicin remains elusive. In cultured cardiac myocytes, doxorubicin induced oxidative stress, DNA damage, ATM activation, and p53 induction. A free radical scavenger NAC attenuated all of these events, whereas an ATM kinase inhibitor wortmannin attenuated doxorubicin-induced ATM activation and p53 induction but not oxidative stress. Doxorubicin treatment in vivo also induced oxidative stress, DNA damage, ATM activation, and p53 accumulation. These observations suggest that p53 induction by doxorubicin is mediated by oxida... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882886 Tue, 04 Aug 2009 23:00:00 +0100 2882886 http://www.medworm.com/index.php?rid=3145799&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003125%2Fabstract%3Frss%3Dyes Abstract: Mutations in multiple genes have been implicated in familial atrial fibrillation (AF), but the underlying mechanisms, and thus implications for therapy, remain ill-defined. Among 231 participants in the Vanderbilt AF Registry, we found a mutation in KCNQ1 (encoding the α-subunit of slow delayed rectifier potassium current [IKs]) and separately a mutation in natriuretic peptide precursor A (NPPA) gene (encoding atrial natriuretic peptide, ANP), both segregating with early onset lone AF in different kindreds. The functional effects of these mutations yielded strikingly similar IKs “gain-of-function.” In Chinese Hamster Ovary (CHO) cells, coexpression of mutant KCNQ1 with its ancillary subunit KCNE1 generated ∼3-fold larger currents that activated much faster than wild-type (... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145799 Mon, 03 Aug 2009 00:00:00 +0100 3145799 http://www.medworm.com/index.php?rid=3258707&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003149%2Fabstract%3Frss%3Dyes Abstract: The remodeling of a heart ventricle after myocardial infarction involves numerous inflammatory mediators that may trigger a long-lasting and a highly fibrogenic process. Likewise, in the kidney, acute and chronic injuries may lead to abnormal extracellular matrix deposition and eventually lead to the loss of renal function. Major breakthroughs have emerged during the last ten years with respect to the pathophysiology of matrix remodeling. Epithelial and endothelial cells are plastic, and able to engage in epithelial (or endothelial)-to-mesenchymal transition (EMT or EndMT), thus actively contributing to the fibrogenesis. Members of the fibrinolytic system were demonstrated to possess unsuspected properties and interact with receptors and integrins on endothelial and epithelial ce... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3258707 Fri, 31 Jul 2009 00:00:00 +0100 3258707 http://www.medworm.com/index.php?rid=2882888&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003150%2Fabstract%3Frss%3Dyes Abstract: The sarcolemmal Na+/HCO3− cotransporter (NBC) plays an important role in intracellular pH (pHi) regulation in the heart. In the present work we studied, in isolated cat ventricular myocytes, the role of Angiotensin II (Ang II) and reactive oxygen species (ROS) production as potential activators of the NBC. pHi was measured in single cells in a medium with HCO3− using the fluorescent pH indicator BCECF. The NH4+ pulse method was used to induce an intracellular acid load and the acid efflux (JH) in the presence of the Na+/H+ exchanger blocker HOE642 (10 μM) was calculated as indicator of NBC activity. The following JH data are presented at pHi of 6.8 (⁎ and # indicate p (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882888 Thu, 30 Jul 2009 23:00:00 +0100 2882888 http://www.medworm.com/index.php?rid=2882885&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003137%2Fabstract%3Frss%3Dyes In this study, for the first time we obtained a SERT-knockout (KO) mouse model which reproduces SIDS phenotype. SERT-KO mice were generated by mating SERTCre/+ heterozygous mice. The SERT-KO mouse embryos at the pre-natal stage E18.5 were lacking of SERT mRNA and protein expression in the heart. A premature death of 75% of SERT-KO mice occurred in the first week after birth. LacZ staining of whole mounts and tissue sections of the heart from SERTCre/+;ROSA26R adult mice and E18.5 embryos demonstrated a marked localized expression of SERT in the right ventricle, the conal region, the vasculature, the atrial septum, the ventricular valves, and the sinoatrial node of the conduction system. These data suggest a cardiac phenotype for the sudden death of SERT-KO mice. Histological analysis of he... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882885 Thu, 30 Jul 2009 23:00:00 +0100 2882885 http://www.medworm.com/index.php?rid=2645099&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003058%2Fabstract%3Frss%3Dyes (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2645099 Tue, 28 Jul 2009 12:38:00 +0100 2645099 http://www.medworm.com/index.php?rid=2645087&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002892%2Fabstract%3Frss%3Dyes (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2645087 Tue, 28 Jul 2009 12:37:59 +0100 2645087 http://www.medworm.com/index.php?rid=3145800&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003095%2Fabstract%3Frss%3Dyes Abstract: To examine the electrophysiological and molecular properties of the transient outward current (Ito) in canine left ventricle using a novel Ito activator, NS5806, Ito was measured in isolated epicardial (Epi), midmyocardial (Mid) and endocardial (Endo) cells using whole-cell patch-clamp techniques. NS5806 activation of Kv4.3 current was also studied in CHO-K1 cells and Xenopus laevis oocytes. In CHO-K1 cells co-transfected with Kv4.3 and KChIP2, NS5806 (10 μM) caused a 35% increase in current amplitude and a marked slowing of current decay with τ increasing from 7.0±0.4 to 10.2±0.3 ms. In the absence of KChIP2, current decay was unaffected by NS5806. In ventricular myocytes, NS5806 increased Ito density by 80%, 82%, and 16% in Epi, Mid, and Endo myocytes, respectively (at +4... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145800 Mon, 27 Jul 2009 00:00:00 +0100 3145800 http://www.medworm.com/index.php?rid=3145790&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002855%2Fabstract%3Frss%3Dyes This article reviews the information obtained to date with the application of cardiac ion-channel expression profiling. With increasing availability and efficiency of high-throughput PCR methods for ion-channel subunit mRNA-expression characterization, it is likely that the application of ion-channel expression profiling will increase and that it will provide important new insights into the determinants of cardiac electrical function in both physiological and pathological situations. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145790 Mon, 27 Jul 2009 00:00:00 +0100 3145790 http://www.medworm.com/index.php?rid=2882881&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003113%2Fabstract%3Frss%3Dyes Abstract: Small-conductance calcium-activated potassium channels (SK channels) have a significant role in neurons. Since they directly integrate calcium handling with repolarization, in heart their role would be particularly important. However, their contribution to cardiac repolarization is still unclear. A previous study reported a significant lengthening effect of apamin, a selective SK channel inhibitor, on the action potential duration in atrial and ventricular mouse cardiomyocytes and human atrial cells. They concluded that these channels provide an important functional link between intracellular calcium handling and action potential kinetics. These findings seriously contradict our studies on cardiac “repolarization reserve”, where we demonstrated that inhibition of a potassium ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882881 Sun, 26 Jul 2009 23:00:00 +0100 2882881 http://www.medworm.com/index.php?rid=3258708&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003083%2Fabstract%3Frss%3Dyes Abstract: The dynamic alterations in the cardiac extracellular matrix following myocardial infarction not only determine the mechanical properties of the infarcted heart, but also directly modulate the inflammatory and reparative response. During the inflammatory phase of healing, rapid activation of Matrix Metalloproteinases (MMP) causes degradation of the cardiac extracellular matrix. Matrix fragments exert potent pro-inflammatory actions, while MMPs process cytokines and chemokines altering their biological activity. In addition, vascular hyperpermeability results in extravasation of fibronectin and fibrinogen leading to formation of a plasma-derived provisional matrix that serves as a scaffold for leukocyte infiltration. Clearance of the infarct from dead cells and matrix debris is ess... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3258708 Fri, 24 Jul 2009 00:00:00 +0100 3258708 http://www.medworm.com/index.php?rid=2882889&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809003071%2Fabstract%3Frss%3Dyes Abstract: Sarcolipin (SLN) has emerged as an important regulator of the atrial sarcoplasmic reticulum (SR) Ca2+ transport. The inhibitory effect of SLN on cardiac SR Ca2+ ATPase (SERCA) pump can be relieved by β-adrenergic stimulation, which indicates that SLN is a reversible inhibitor. However, the mechanism of this reversible regulation of SERCA pump by SLN is yet to be determined. In the current study using adult rat ventricular myocytes we provide evidence that the threonine 5 (T5) residue at the N-terminus of SLN which is conserved among various species, critically regulates the SLN function. Point mutation of T5→alanine exerts an inhibitory effect on myocyte contractility and calcium transients similar to that of wild-type SLN, whereas mutation of T5→glutamic acid which mimics t... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882889 Thu, 23 Jul 2009 23:00:00 +0100 2882889 http://www.medworm.com/index.php?rid=2761683&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002740%2Fabstract%3Frss%3Dyes Howard E. Morgan, one of the leading experimental cardiologists of the 20th century, died after a brief illness on March 2, 2009 in Estero, Florida. He died of complications of a fall which occurred while he was receiving coumadin therapy for atrial fibrillation. Howard is survived by his wife Donna and a daughter Patricia Morgan Wehler of East Berlin Pa. as well as two grandsons, Jonathan and Geoffrey Morgan of Ann Arbor Michigan. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2761683 Wed, 22 Jul 2009 23:00:00 +0100 2761683 http://www.medworm.com/index.php?rid=3145801&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002867%2Fabstract%3Frss%3Dyes Abstract: Endocannabinoids are amides and esters of long chain fatty acids that can modulate ion channels through both receptor-dependent and receptor-independent effects. Nowadays, their effects on cardiac K+ channels are unknown even when they can be synthesized within the heart. We have analyzed the direct effects of endocannabinoids, such as anandamide (AEA), 2-arachidonoylglycerol (2-AG), the endogenous lipid lysophosphatidylinositol, and cannabinoid analogues such as palmitoylethanolamide (PEA), and oleoylethanolamide, as well as the fatty acids from which they are endogenously synthesized, on human cardiac Kv4.3 channels, which generate the transient outward K+ current (Ito1). Currents were recorded in Chinese hamster ovary cells, which do not express cannabinoid receptors, by using... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145801 Tue, 21 Jul 2009 00:00:00 +0100 3145801 http://www.medworm.com/index.php?rid=3145780&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228280900306X%2Fabstract%3Frss%3Dyes Abstract: Rapidly activating and inactivating cardiac transient outward K+ currents, Ito, are expressed in most mammalian cardiomyocytes, and contribute importantly to the early phase of action potential repolarization and to plateau potentials. The rapidly recovering (Ito,f) and slowly recovering (Ito,s) components are differentially expressed in the myocardium, contributing to regional heterogeneities in action potential waveforms. Consistent with the marked differences in biophysical properties, distinct pore-forming (α) subunits underlie the two Ito components: Kv4.3/Kv4.2 subunits encode Ito,f, whereas Kv1.4 encodes Ito,s, channels. It has also become increasingly clear that cardiac Ito channels function as components of macromolecular protein complexes, comprising (four) Kvα subuni... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145780 Tue, 21 Jul 2009 00:00:00 +0100 3145780 http://www.medworm.com/index.php?rid=2761684&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002843%2Fabstract%3Frss%3Dyes The sarcomeric Z-disc is one of the most complex macromolecular structures in biology . Some of its constituents have important structural functions and an increasing number of recent publications point to additional, previously unexpected features. A new view is now emerging, whereby Z-disc proteins are involved as important intra- and intercellular signaling nodes . Translocation of Z-disc proteins to the nucleus and probably to the M-band as well as to other compartments, their interaction with additional signaling molecules and ability to facilitate macromolecular protein complexes are only a few properties to indicate their multi-functionality. In this context it was shown, that I-band proteins such as FHL1 or muscle ankyrin repeat proteins such as CARP as well as the titin kinase, wh... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2761684 Mon, 20 Jul 2009 23:00:00 +0100 2761684 http://www.medworm.com/index.php?rid=2761695&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228280900282X%2Fabstract%3Frss%3Dyes Abstract: We have previously reported that administration of granulocyte colony-stimulating factor (G-CSF)+Flt-3 ligand (FL) or G-CSF+stem cell factor (SCF) improves left ventricular (LV) function and halts LV remodeling at 35 d after myocardial infarction (MI). In the current study, we investigated whether these beneficial effects are sustained in the long term — an issue of fundamental importance for clinical translation. Mice undergoing a 30-min coronary occlusion followed by reperfusion received vehicle (group I), G-CSF+FL (group II), G-CSF+SCF (group III), or G-CSF alone (group IV) starting 4 h after reperfusion and were euthanized 48 wk later. LV structure and function were assessed by serial echocardiography before and at 48 h and 4, 8, 16, 32, and 48 wk after MI. During foll... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2761695 Thu, 16 Jul 2009 23:00:00 +0100 2761695 http://www.medworm.com/index.php?rid=2761693&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002831%2Fabstract%3Frss%3Dyes This study was designed to test the hypothesis that insulin inhibits adherence of polymorphonuclear leukocytes (PMNs) to endothelial cells in myocardial ischemia/reperfusion (MI/R) and to investigate the underlying mechanisms. Anesthetized rabbits were subjected to MI/R (45 min/4 h) and randomly received saline, glucose-insulin-potassium (GIK) or GK respectively (2 mL/kg/h, i.v.). In vitro study was performed on cultured endothelial cells subjected to simulated ischemia/reperfusion. In vivo treatment with GIK but not GK attenuated myocardial injury as evidenced by reduced plasma creatine kinase activity, myocardial apoptosis and infarct size in MI/R rabbits compared with the saline group. Interestingly, GIK but not GK significantly decreased coronary endothelial expression of P-selectin... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2761693 Thu, 16 Jul 2009 23:00:00 +0100 2761693 http://www.medworm.com/index.php?rid=2761686&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228280900279X%2Fabstract%3Frss%3Dyes Abstract: In this article, we review the biophysical basis and functional implications of a novel Ca2+ signal (called “Ca2+ sparklets”) produced by Ca2+ influx via L-type Ca2+ channels (LTCCs) in smooth muscle. Ca2+ sparklet activity is bimodal. In low activity mode, Ca2+ sparklets are produced by random, brief openings of solitary LTCCs. In contrast, small clusters of LTCCs can function in a high activity mode that creates sites of continual Ca2+ influx called “persistent Ca2+ sparklets”. Low activity and persistent Ca2+ sparklets contribute to Ca2+ influx in arterial, colonic, and venous smooth muscle. Targeting of PKCα by the scaffolding protein AKAP150 to specific sarcolemmal domains is required for the activation of persistent Ca2+ sparklets. Calcineurin, which is also associ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2761686 Thu, 16 Jul 2009 23:00:00 +0100 2761686 http://www.medworm.com/index.php?rid=3258709&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002788%2Fabstract%3Frss%3Dyes Abstract: Extracellular matrix disturbances play an important role in the development of ventricular remodeling and failure. Genetically modified mice with abnormalities in the synthesis and degradation of extracellular matrix have been generated, in particular mice with deletion or overexpression of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs). Echocardiography is ideally suited to serially evaluate left ventricular (LV) size and function, thus defining the progression of LV remodeling and failure. This Review describes the echocardiographic parameters that may provide insights into the development of ventricular remodeling and heart failure. The application of echocardiography to study LV remodeling and function after myocardial infarction a... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3258709 Thu, 16 Jul 2009 00:00:00 +0100 3258709 http://www.medworm.com/index.php?rid=3145803&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002776%2Fabstract%3Frss%3Dyes In conclusion, this study revealed that 5-HT4 (mainly 5-HT4b), 5-HT2A and 5-HT2B receptors coexisted in auricular myocytes of newborn rat, that 5-HT4 activation reduced cAMP concentration, ICaL and intercellular coupling whereas 5-HT2A or 5-HT2B activation conversely enhanced GJIC. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145803 Thu, 16 Jul 2009 00:00:00 +0100 3145803 http://www.medworm.com/index.php?rid=3145802&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002818%2Fabstract%3Frss%3Dyes Abstract: Native volume-sensitive outwardly rectifying anion channels (VSOACs) play a significant role in cell volume homeostasis in mammalian cells. However, the molecular correlate of VSOACs has been elusive to identify. The short isoform of ClC-3 (sClC-3) is a member of the mammalian ClC gene family and has been proposed to be a molecular candidate for VSOACs in cardiac myocytes and vascular smooth muscle cells. To directly test this hypothesis, and assess the physiological role of ClC-3 in cardiac function, we generated a novel line of cardiac-specific inducible ClC-3 knock-out mice. These transgenic mice were maintained on a doxycycline diet to preserve ClC-3 expression; removal of doxycycline activates Cre recombinase to inactivate the Clcn3 gene. Echocardiography revealed dramatical... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145802 Thu, 16 Jul 2009 00:00:00 +0100 3145802 http://www.medworm.com/index.php?rid=2882887&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002764%2Fabstract%3Frss%3Dyes Abstract: Emerging evidence from large animal models implicates Ca2+ regulation, particularly intracellular sarcoplasmic reticulum (SR) Ca2+ release, as essential for sinoatrial node (SAN) automaticity. However, despite the apparent importance of SR Ca2+ release to SAN cell function it is uncertain how SR Ca2+ release is controlled in SAN cells from mouse. Understanding mouse SAN SR Ca2+ release mechanism will allow improved understanding of results in studies on SAN from genetic mouse models of Ca2+ homeostatic proteins. Here we investigated the functional relationship between sarcolemmal Ca2+ influx and SR Ca2+ release at the level of single SAN cell, using simultaneous patch-clamp current recording and high resolution confocal Ca2+ imaging techniques. In mouse SAN cells, both Ca2+ chann... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2882887 Wed, 15 Jul 2009 23:00:00 +0100 2882887 http://www.medworm.com/index.php?rid=2761690&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002806%2Fabstract%3Frss%3Dyes Abstract: During atrial fibrillation (AF), rapid stimulation causes atrial remodeling that increases arrhythmia susceptibility. Using an established atrial (HL-1) myocyte model, we investigated the transcriptional profile associated with early atrial myocyte remodeling. Spontaneously contracting HL-1 cells were cultured in the absence and presence of rapid stimulation for 24 h  and RNA harvested for microarray analysis. We identified 758 genes that were significantly altered with rapid stimulation (626 up- and 132 down-regulated). Results were confirmed using real-time quantitative RT-PCR for selected genes based on physiological relevance in human AF and/or experimental atrial tachycardia (AT), and regulation in the microarray results. In some cases, transcriptional changes were rapid, ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2761690 Wed, 15 Jul 2009 23:00:00 +0100 2761690 http://www.medworm.com/index.php?rid=3145786&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002752%2Fabstract%3Frss%3Dyes Abstract: Reconstitution of KATP channel activity from coexpression of members of the pore-forming inward rectifier gene family (Kir6.1, KCNJ8, and Kir6.2 KCNJ11) with sulfonylurea receptors (SUR1, ABCC8, and SUR2, ABCC9) of the ABCC protein sub-family, has led to the elucidation of many details of channel gating and pore properties, as well as the essential roles of Kir6.2 and SUR2 subunits in generating cardiac ventricular KATP. However, despite this extensive body of knowledge, there remain significant holes in our understanding of the physiological role of the cardiac KATP channel, and surprising new findings keep emerging. Recent findings from genetically modified animals include the apparent insensitivity of cardiac sarcolemmal channels to nucleotide levels, and unenvisioned complexi... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145786 Wed, 15 Jul 2009 00:00:00 +0100 3145786 http://www.medworm.com/index.php?rid=3258711&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002715%2Fabstract%3Frss%3Dyes Abstract: In diabetes mellitus, alterations in cardiac structure/function in the absence of ischemic heart disease, hypertension or other cardiac pathologies are termed diabetic cardiomyopathy. In the United States, the prevalence of diabetes mellitus continues to rise and the disease currently affects about 8% of the general population. Hence, the use of appropriate diagnostic strategies for diabetic cardiomyopathy, which may help correctly identify the disease at early stages and implement suitable corrective therapies is imperative. Currently, there is no single diagnostic method for the identification of diabetic cardiomyopathy. Diabetic cardiomyopathy is known to induce changes in cardiac structure such as, myocardial hypertrophy, fibrosis and fat droplet deposition. Early changes in ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3258711 Mon, 13 Jul 2009 00:00:00 +0100 3258711 http://www.medworm.com/index.php?rid=3258710&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002739%2Fabstract%3Frss%3Dyes Abstract: The review describes the role of loose connective tissues with focus on transcapillary exchange and edema formation with relevance for inflammation, fibrosis and tumors. Based on studies in these tissues, comparisons are made to the fibrotic processes in the heart. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3258710 Mon, 13 Jul 2009 00:00:00 +0100 3258710 http://www.medworm.com/index.php?rid=2761696&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002727%2Fabstract%3Frss%3Dyes Abstract: Peroxisome proliferator-activated receptor δ (PPARδ) is an essential determinant of basal myocardial fatty acid oxidation (FAO) and bioenergetics. We wished to determine whether increased lipid loading affects the PPARδ deficient heart in transcriptional regulation of FAO and in the development of cardiac pathology. Cardiomyocyte-restricted PPARδ knockout (CR-PPARδ−/−) and control (α-MyHC-Cre) mice were subjected to 48 h of fasting and to a long-term maintenance on a (28 weeks) high-fat diet (HFD). The expression of key FAO proteins in heart was examined. Serum lipid profiles, cardiac pathology, and changes of various transduction signaling pathways were also examined. Mice subjected to fasting exhibited upregulated transcript expression of FAO genes in the CR-PPARδ�... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2761696 Sun, 12 Jul 2009 23:00:00 +0100 2761696 http://www.medworm.com/index.php?rid=3145784&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002697%2Fabstract%3Frss%3Dyes Abstract: In mammals cardiac rate is determined by the duration of the diastolic depolarization of sinoatrial node (SAN) cells which is mainly determined by the pacemaker If current. f-channels are encoded by four members of the hyperpolarization-activated cyclic nucleotide-gated gene (HCN1–4) family. HCN4 is the most abundant isoform in the SAN, and its relevance to pacemaking has been further supported by the discovery of four loss-of-function mutations in patients with mild or severe forms of cardiac rate disturbances. Due to its selective contribution to pacemaking, the If current is also the pharmacological target of a selective heart rate-reducing agent (ivabradine) currently used in the clinical practice. Albeit to a minor extent, the If current is also present in other spontaneou... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3145784 Thu, 09 Jul 2009 00:00:00 +0100 3145784 http://www.medworm.com/index.php?rid=2761689&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002703%2Fabstract%3Frss%3Dyes In conclusion, CaMKII constitutively regulates cardiac Na+ channel and this regulatory mechanism is important for the maintenance of Na+ channel characteristics under physiological conditions. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2761689 Wed, 08 Jul 2009 23:00:00 +0100 2761689 http://www.medworm.com/index.php?rid=3258714&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228280900265X%2Fabstract%3Frss%3Dyes Abstract: The cardiac interstitium is a unique and adaptable extracellular matrix (ECM) that provides a milieu in which myocytes, fibroblasts, and endothelial cells communicate and function. The composition of the ECM in the heart includes structural proteins such as fibrillar collagens and matricellular proteins that modulate cell:ECM interaction. Secreted Protein Acidic and Rich in Cysteine (SPARC), a collagen-binding matricellular protein, serves a key role in collagen assembly into the ECM. Recent results demonstrated increased cardiac rupture, dysfunction and mortality in SPARC-null mice in response to myocardial infarction that was associated with a decreased capacity to generate organized, mature collagen fibers. In response to pressure overload induced-hypertrophy, the decrease in ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3258714 Mon, 06 Jul 2009 00:00:00 +0100 3258714 http://www.medworm.com/index.php?rid=3258713&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002661%2Fabstract%3Frss%3Dyes Abstract: Remodeling after myocardial infarction (MI) associates with left ventricular (LV) dilation, decreased cardiac function and increased mortality. The dynamic synthesis and breakdown of extracellular matrix (ECM) proteins play a significant role in myocardial remodeling post-MI. Expression of osteopontin (OPN) increases in the heart post-MI. Evidence has been provided that lack of OPN induces LV dilation which associates with decreased collagen synthesis and deposition. Inhibition of matrix metalloproteinases, key players in ECM remodeling process post-MI, increased ECM deposition (fibrosis) and improved LV function in mice lacking OPN after MI. This review summarizes — 1) signaling pathways leading to increased expression of OPN in the heart; 2) the alterations in the structure a... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3258713 Wed, 01 Jul 2009 00:00:00 +0100 3258713 http://www.medworm.com/index.php?rid=3258712&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002685%2Fabstract%3Frss%3Dyes Abstract: Cardiac remodeling is accelerated during pathological conditions and several anabolic and catabolic regulators work in concert to repair the myocardium and maintain its functionality. The fibroblasts play a major role in this process via collagen deposition as well as supplying the degradative matrix metalloproteinases. During the more acute responses to a myocardial infarction (MI) the heart relies on a more aggressive wound healing sequence that includes the myofibroblasts, specialized secretory cells necessary for infarct scar formation and thus, rescue of the myocardium. The activated fibroblasts and myofibroblasts deposit large amounts of fibrillar collagen during the post-MI wound healing phase, type I and III collagen are the most abundant collagens in the heart and they m... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=3258712 Wed, 01 Jul 2009 00:00:00 +0100 3258712 http://www.medworm.com/index.php?rid=2761691&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002673%2Fabstract%3Frss%3Dyes This study found an augmented negative inotropic and lusitropic response to administration of agonists selective for the kappa opioid receptor and delta opioid receptor in the failing heart that was mediated by a pertussis toxin-sensitive G-protein. The augmented decrease in cardiac function was manifested by increased inhibition of cAMP accumulation and the amplitude of the systolic Ca2+ transient. Furthermore, increased depression of cardiac function and of two important second messengers, cAMP and intracellular Ca2+, were independent of changes in cardiac opioid peptide or receptor expression. Thus, the cardiomyopathy-induced failing heart experiences increased cardiac depressant effects following opioid receptor stimulation which could exacerbate diminished cardiac function in end-stag... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2761691 Tue, 30 Jun 2009 23:00:00 +0100 2761691 http://www.medworm.com/index.php?rid=2761688&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002648%2Fabstract%3Frss%3Dyes Abstract: Decades of intensive research of primary cardiac pacemaker, the sinoatrial node, have established potential roles of specific membrane channels in the generation of the diastolic depolarization, the major mechanism allowing sinoatrial node cells to generate spontaneous beating. During the last three decades, multiple studies made either in the isolated sinoatrial node or sinoatrial node cells have demonstrated a pivotal role of Ca2+ and, specifically Ca2+ release from sarcoplasmic reticulum, for spontaneous beating of cardiac pacemaker. Recently, spontaneous, rhythmic local subsarcolemmal Ca2+ releases from ryanodine receptors during late half of the diastolic depolarization have been implicated as a vital factor in the generation of sinoatrial node cell spontaneous firing. Local... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2761688 Tue, 30 Jun 2009 23:00:00 +0100 2761688 http://www.medworm.com/index.php?rid=2552824&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282809002429%2Fabstract%3Frss%3Dyes (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=2552824 Mon, 29 Jun 2009 16:50:37 +0100 2552824