Calcium and Excitation-Contraction Coupling in the Heart

Abstract

Cardiac contractility is regulated by changes in intracellular Ca concentration ([Ca2+]i). Normal function requires that [Ca2+]i be sufficiently high in systole and low in diastole. Much of the Ca needed for contraction comes from the sarcoplasmic reticulum and is released by the process of calcium-induced calcium release. The factors that regulate and fine-tune the initiation and termination of release are reviewed. The precise control of intracellular Ca cycling depends on the relationships between the various channels and pumps that are involved. We consider 2 aspects: (1) structural coupling: the transporters are organized within the dyad, linking the transverse tubule and sarcoplasmic reticulum and ensuring close proximity of Ca entry to sites of release. (2) Functional coupling: where the fluxes across all membranes must be balanced such that, in the steady state, Ca influx equals Ca efflux on every beat. The remainder of the review considers specific aspects of Ca signaling, including the role of Ca buffers, mitochondria, Ca leak, and regulation of diastolic [Ca2+]i.

Long-Term Oral Administration of Theaphenon-E Improves Cardiomyocyte Mechanics and Calcium Dynamics by Affecting Phospholamban Phosphorylation and ATP Production

“…It is known that the activity of SERCA2 is reversibly regulated by PLB, a 52 amino acid phosphoprotein [27,45]. Dephosphorylated PLB interacts with SERCA2 and inhibits the pumping activity, whereas phosphorylation of PLB relieves the inhibitory effects resulting in increased calcium re-uptake into the SR and enhanced contractility [46], as we actually observed.…”

“…SERCA2 activity is mainly modulated by a small protein, the PLB. The phosphorylation status of PLB (p-PLB) is able to remove the inhibitory effect of PLB on SERCA2, resulting in increased SR-Ca 2+ uptake and enhanced myocyte contractility and relaxation [27]. We have actually measured a marked decrease in the total PLB (-23%, p=0.08; Fig.…”

“…This proximity results in a transient exposure of mitochondrial Ca 2+ uniporter to high concentrations of Ca 2+ following Ca 2+ release from the SR favouring the influx of the ion into mitochondria. Mitochondrial calcium accumulation triggers the activation of the metabolic machinery, which increases ATP synthesis in the mitochondria and, hence, ATP levels in the cytosol [27]. It is conceivable that the higher amplitude of the calcium transient measured in GTE cells compared to CTRL might amplify this process, resulting in increased mitochondria ATP production.…”

Intracellular Calcium Regulation in Canine Ventricular Myocytes: a Simulation Study

“…Intracellular calcium handling is a key process in the electrophysiology of cardiac myocytes [1,2]. On the one hand, it determines cell contractility [1], because intracellular calcium is the main regulator of myocardial excitation-contraction coupling.…”

“…On the one hand, it determines cell contractility [1], because intracellular calcium is the main regulator of myocardial excitation-contraction coupling. On the other hand, it is intimately related to arrhythmogenesis, because calcium overload may trigger abnormal cell depolarization [2,3].…”