Calcium Cycling and Signaling in Cardiac Myocytes
ABSTRACT Calcium (Ca) is a universal intracellular second messenger. In muscle, Ca is best known for its role in contractile activation. However, in recent years the critical role of Ca in other myocyte processes has become increasingly clear. This review focuses on Ca signaling in cardiac myocytes as pertaining to electrophysiology (including action potentials and arrhythmias), excitation-contraction coupling, modulation of contractile function, energy supply-demand balance (including mitochondrial function), cell death, and transcription regulation. Importantly, although such diverse Ca-dependent regulations occur simultaneously in a cell, the cell can distinguish distinct signals by local Ca or protein complexes and differential Ca signal integration.
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ABSTRACT: Cardiomyocyte function depends on coordinated movements of calcium into and out of the cell and the proper delivery of ATP to energy-utilizing enzymes. Defects in calcium-handling proteins and abnormal energy metabolism are features of heart failure. Recent discoveries have led to gene-based therapies targeting calcium-transporting or -binding proteins, such as the cardiac sarco(endo)plasmic reticulum calcium ATPase (SERCA2a), leading to improvements in calcium homeostasis and excitation-contraction coupling. Here we review impaired calcium cycling and energetics in heart failure, assessing their roles from both a mutually exclusive and interdependent viewpoint, and discuss therapies that may improve the failing myocardium. Copyright © 2015 Elsevier Inc. All rights reserved.Cell Metabolism 02/2015; 21(2):183-194. DOI:10.1016/j.cmet.2015.01.005 · 16.75 Impact Factor
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ABSTRACT: Cytosolic calcium concentration ([Ca2+]c) is fundamental for regulation of many cellular processes such metabolism, proliferation, muscle contraction, cell signaling and insulin secretion. In resting conditions, the sarco/endoplasmic reticulum (ER/SR) Ca2+ ATPase’s (SERCA) transport Ca2+ from the cytosol to the ER or SR lumen, maintaining the resting [Ca2+]c about 25-100 nM. A reduced activity/expression of SERCA2 protein has been described in heart failure and diabetic cardiomyopathy, resulting in an altered Ca2+ handling and cardiac contractility. In the diabetic pancreas, has been reported reduction in SERCA2b and SERCA3 expression in β-cells, resulting in diminished insulin secretion. Evidence obtained from different diabetes models have suggested a role for advanced glycation end products formation, oxidative stress and increased O-GlcNAcylation in the lowered SERCA2 expression observed in diabetic cardiomyopathy. However, the role of SERCA2 down-regulation in the pathophysiology of diabetes mellitus and diabetic cardiomyopathy is not yet well described. In this review, we make a comprehensive analysis of the current knowledge of the role of the SERCA pumps in the pathophysiology of insulin-dependent diabetes mellitus type 1 (TIDM) and type 2 (T2DM) in the heart and β-cells in the pancreasCell calcium 09/2014; DOI:10.1016/j.ceca.2014.09.005 · 4.21 Impact Factor
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ABSTRACT: Diabetes mellitus is one of the most common medical conditions. It is associated to medical complications in numerous organs and tissues, of which the heart is one of the most important and most prevalent organs affected by this disease. In fact, cardiovascular complications are the most common cause of death among diabetic patients. At the end of the 19th century, the weakness of the heart in diabetes was noted as part of the general muscular weakness that exist in that disease. However, it was only in the eighties that diabetic cardiomyopathy was recognized, which comprises structural and functional abnormalities in the myocardium in diabetic patients even in the absence of coronary artery disease or hypertension. This disorder has been associated with both type 1 and type 2 diabetes, and is characterized by early-onset diastolic dysfunction and late-onset systolic dysfunction, in which alteration in Ca2+ signaling is of major importance, since it controls not only contraction, but also excitability (and therefore is involved in rhythmic disorder), enzymatic activity, and gene transcription. Here we attempt to give a brief overview of Ca2+ fluxes alteration reported on diabetes, and provide some new data on differential modulation of Ca2+ handling alteration in males and females type 2 diabetic mice to promote further research. Due to space limitations, we apologize for those authors whose important work is not cited.Cell Calcium 08/2014; DOI:10.1016/j.ceca.2014.08.004 · 4.21 Impact Factor