Figure 1.

Excitation–contraction coupling. During systole, the action potential depolarizes the sarcolemma. This depolarization enables a small amount of extracellular Ca²⁺ to enter the cytosol through the LTCCs. Ca²⁺ entry triggers the release of Ca²⁺ from the SR through RyR2 channels. The intracellular Ca²⁺ concentration increases and binding of Ca²⁺ to TN-C activates myofilaments, resulting in muscle contraction. Removal of cytosolic Ca²⁺ during diastole is primarily facilitated by SERCA2a, which returns Ca²⁺ to the SR. Some Ca²⁺ also exits the cell through NCX. The decrease in intracellular Ca²⁺ leads to dissociation of Ca²⁺ from TN-C and muscle relaxation. Abbreviations: LTCC, voltage-dependent L-type Ca²⁺ channel; NCX, Na⁺/Ca²⁺ exchanger; RyR2, ryanodine receptor 2; SERCA2, sarcoplasmic/endoplasmic reticulum calcium ATPase 2; SR, sarcoplasmic reticulum; TN-C, troponin C.