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.
"Cyclic adenosine 3 ′ ,5 ′ -monophosphate (cAMP) is the main second messenger of the β-adrenergic receptor signaling inducing phosphorylation of the LTCC and the ryanodine receptor to increase the amount of intracellular Ca 2+ necessary for heart contractility (responsible for positive chronotropic and inotropic effects during sympathetic stimulation) (Guellich et al., 2014). Moreover, catecholamine stimulated β-adrenergic receptor not only leads to cAMP effector dependent-troponin I phosphorylation to allow faster force development and shortening during systole and faster force relaxation and re-lengthening during diastole but also mediated cAMP effector dependent-phospholamban phosphorylation responsible for Ca 2+ re-uptake in the sarcoplasmic reticulum and myofilament relaxation (lusitropic effects) (Bers, 2008). However sustained stimulation of this pathway may be detrimental thus leading to cardiac remodeling and development of heart failure (Brodde, 1993; Kiuchi et al., 1993). "
[Show abstract][Hide abstract] ABSTRACT: Cyclic adenosine 3',5'-monophosphate (cAMP) modulates a broad range of biological processes including the regulation of cardiac myocyte contractile function where it constitutes the main second messenger for β-adrenergic receptors' signaling to fulfill positive chronotropic, inotropic and lusitropic effects. A growing number of studies pinpoint the role of spatial organization of the cAMP signaling as an essential mechanism to regulate cAMP outcomes in cardiac physiology. Here, we will briefly discuss the complexity of cAMP synthesis and degradation in the cardiac context, describe the way to detect it and review the main pharmacological arsenal to modulate its availability.
Frontiers in Pharmacology 10/2015; 6. DOI:10.3389/fphar.2015.00203 · 3.80 Impact Factor
"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). "
"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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