Excitation–Contraction Coupling of Cardiomyocytes

Abstract

Cardiomyocytes are electrically excitable cells built to contract. The cellular processes linking electrical excitation, i.e. the sarcolemmal action potential, with contraction are referred to as excitation–contraction coupling. An increase in intracellular Ca2+ concentration ([Ca2+]i) is the key mediator of excitation–contraction coupling. Cardiac action potentials are characterised by a long plateau phase carried by Ca2+ influx through L-type Ca2+ channels. L-type Ca2+ influx triggers Ca2+ release from the sarcoplasmic reticulum (SR) through Ca2+ release channels or ryanodine receptors. This Ca2+-induced Ca2+ release causes a large increase in [Ca2+]i from ≈ 100 nM in diastole to ≈ 1 μM in systole. Ca2+ binding to the myofilaments causes contraction. Ca2+ removal from the cytosol by the SR-Ca2+-ATPase (SERCA) and the sarcolemmal Na+–Ca2+ exchanger (NCX) mediates relaxation. The amplitude of the [Ca2+]i transient (CaT) decides about the strength of contraction. Increases in L-type Ca2+ current, SERCA activity, SR Ca2+ load and fractional release, IP3 signalling and [Na+]i all increase CaT amplitude. Under conditions of Ca2+ overload, SR Ca2+ release also occurs spontaneously, i.e. in the absence of an action potential, and may elicit life-threatening arrhythmias via activation of electrogenic NCX and subsequent membrane depolarisation. Atrial and ventricular myocytes share these basic principles of excitation–contraction coupling and [Ca2+]i regulation. However, there are important differences between these types of cardiomyocytes regarding action potential configuration, sarcolemmal structure (transverse tubules) and subcellular Ca2+ regulation. Remodelling of excitation–contraction coupling occurs in cardiac disease such as heart failure and atrial fibrillation and represents a potential therapeutic target.