Figure 1.

Schematic diagram of excitation-contraction coupling in the ventricular cardiomyocyte. (1) Sarcolemmal depolarization causes L-type Ca²⁺ channels (LTCC) to open, resulting in influx of Ca²⁺ during systole. Ca²⁺ enters initially through the LTCC. (2) During the early stages of the action potential, the Na⁺–Ca²⁺ exchanger (NCX) also transitions from functioning in forward mode (Na⁺ in Ca²⁺ out) to reverse mode (Ca²⁺ in Na⁺ out) to further enhance the rise in [Ca²⁺]_i. (3) The initial rise in [Ca²⁺]_i induces a larger release of Ca²⁺ from the sarcoplasmic reticulum (SR) via ryanodine receptors (RyR2), resulting in a large rise in [Ca²⁺]_i. (4) The large rise in Ca²⁺ causes contraction of the myofilaments. (5) [Ca²⁺] is subsequently reduced to bring about diastole through movement out of the cytosol (a) via NCX in forward mode and (b) the sarcolemmal Ca²⁺-ATPase. (c) Ca²⁺ is also buffered by mitochondria. (d) The majority of Ca²⁺ movement in diastole is into the SR via SERCA2a. Green arrows denote transitions brought about by sarcolemmal depolarization. Black arrows denote routes of influx of Ca²⁺ to the cytosol during systole. Purple arrow denotes contraction of myofilaments. Red arrows denote routes of efflux of Ca²⁺ during diastole.