Cardiomyocyte calcium homeostasis

Cardiomyocyte calcium homeostasis is the complex physiological process that regulates the concentration and movement of calcium ions (Ca2+) within cardiac muscle cells, serving as the bridge between electrical excitation and mechanical contraction, known as excitation-contraction coupling (ECC) (Bers, 2002, Nature). This system relies on the coordinated activity of several key proteins: L-type calcium channels (LTCC) facilitate initial Ca2+ entry, which triggers a larger release of Ca2+ from the sarcoplasmic reticulum (SR) via ryanodine receptors (RyR2) (Eisner et al., 2017, Circ Res). For relaxation to occur, Ca2+ must be removed from the cytoplasm, primarily through reuptake into the SR by the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) and extrusion via the sodium-calcium exchanger (NCX) (Marks, 2013, JCI). Dysregulation of these pathways, such as leaky RyR2 channels or reduced SERCA2a activity, is a primary driver of contractile dysfunction in heart failure and provides a substrate for triggered arrhythmias (Landstrom et al., 2017, Nat Rev Cardiol). Therapeutic strategies targeting this process include calcium channel blockers to manage rhythm and pressure, as well as emerging therapies like RyR2 stabilizers and SERCA2a activators aimed at restoring efficient calcium cycling.

Other names

Excitation-contraction couplingCardiac calcium signalingCalcium handling in cardiomyocytes

Modulation of calcium entry via L-type channels, stabilization of ryanodine receptors to prevent diastolic leak, enhancement of SERCA2a-mediated calcium reuptake, and sensitization of myofilaments to calcium.