Calcium Cycling and Signaling in Cardiac Myocytes

Department of Physiology and Cardiovascular Institute, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
Annual Review of Physiology (Impact Factor: 18.51). 02/2008; 70(1):23-49. DOI: 10.1146/annurev.physiol.70.113006.100455
Source: PubMed

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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    • "This approximately 10-fold increase in cytosolic calcium concentration activates calcium-sensitive contractile proteins (troponin C; TN-C), which then use ATP to produce tension and muscle contraction. For muscle relaxation to occur, calcium is removed from the cytosol—approximately 30% is transported out of the cell (primarily by the sodium-calcium exchanger [NCX] and plasma membrane calcium ATPase [PMCA]) while 70% is pumped back into the SR via the cardiac SR calcium ATPase (SERCA2a) (Bers, 2008). "
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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 · 17.57 Impact Factor
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    • "These features are similar to those observed in failing human heart specimens and genetic cardiomyopathies (Sun et al., 2012), confirming that the changes in the pattern of sarcomere staining do reflect structural abnormality. As loss of sarcomeric integrity disturbs the close physical coupling between calcium release units and contractile proteins (Bers, 2008), we investigated the functional consequences of sarcomeric disarray. In CMs exposed to DM, the frequency of systolic calcium transients decreased (Figure 2G). "
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    ABSTRACT: Diabetic cardiomyopathy is a complication of type 2 diabetes, with known contributions of lifestyle and genetics. We develop environmentally and genetically driven in vitro models of the condition using human-induced-pluripotent-stem-cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray. Next, we consider genetic effects by deriving cardiomyocytes from two diabetic patients with variable disease progression. The cardiomyopathic phenotype is recapitulated in the patient-specific cells basally, with a severity dependent on their original clinical status. These models are incorporated into successive levels of a screening platform, identifying drugs that preserve cardiomyocyte phenotype in vitro during diabetic stress. In this work, we present a patient-specific induced pluripotent stem cell (iPSC) model of a complex metabolic condition, showing the power of this technique for discovery and testing of therapeutic strategies for a disease with ever-increasing clinical significance. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
    Cell Reports 11/2014; 9(3):810-20. DOI:10.1016/j.celrep.2014.09.055 · 8.36 Impact Factor
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    • "In the heart, the SR plays a key role in the ECC process [5]. In the normal cardiomyocyte SERCA2a actively transports Ca 2+ into the lumen of the SR during relaxation and accounts for approximately 70% of the re-uptake of the Ca 2+ involved in the Ca 2+ transient [3] [4] [5]. "
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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 pancreas
    Cell calcium 09/2014; DOI:10.1016/j.ceca.2014.09.005 · 3.51 Impact Factor
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