Calcium ion homeostasis in cardiomyocyte membrane (ECC)

Calcium ion homeostasis in the cardiomyocyte membrane is the fundamental physiological process governing the contraction and relaxation of the heart muscle (Bers, 2002, Nature). It relies on the orchestrated movement of calcium ions (Ca2+) across the sarcolemma and the sarcoplasmic reticulum (SR) membrane through proteins like the L-type calcium channel (LTCC), ryanodine receptor 2 (RyR2), and the sodium-calcium exchanger (NCX) (Eisner et al., 2017, Circulation Research). In a healthy heart, electrical depolarization triggers Ca2+ entry via LTCCs, which induces a larger Ca2+ release from the SR—a process known as calcium-induced calcium release—leading to myofibril contraction (Marks, 2003, JCI). Relaxation occurs as Ca2+ is sequestered back into the SR by the SERCA2a pump or extruded from the cell by NCX and the plasma membrane Ca2+-ATPase. Disruptions in these mechanisms, such as "leaky" RyR2 channels or reduced SERCA2a activity, are central to the pathogenesis of heart failure and lethal arrhythmias (Landstrom et al., 2017, JCI Insight). Consequently, many cardiovascular drugs, including calcium channel blockers and digitalis glycosides, work by modulating specific components of this homeostatic system to restore cardiac performance or rhythm.

Other names

Excitation-contraction couplingCardiac calcium handlingMyocardial calcium signalingCalcium cyclingSarcolemmal calcium flux

Modulation of transmembrane calcium influx via L-type channels; inhibition of the Na+/K+-ATPase to increase intracellular sodium and decrease calcium extrusion via NCX; stabilization of RyR2 to prevent diastolic calcium leak; and enhancement of myofilament calcium sensitivity.