ABSTRACT
Ca2+ entry into cardiac myocytes is initiated by the cardiac action potential (AP), where depolarization activates inward Ca2+ current (ICa), which in turn contributes to the AP plateau (Fig. 13.1). This Ca2+ entry triggers sarcoplasmic reticulum (SR) Ca2+ release. The combination of ICa and SR Ca2+ release raises intracellular free [Ca2+], ([Ca2+]i), allowing Ca2+ binding to the myofilament protein troponin C, which activates contraction. For relaxation to occur [Ca2+]i must decline, allowing Ca2+ to dissociate from troponin. This requires Ca2+ transport from the cytosol, and four transport pathways can contribute to this transport process: (1) SR Ca2+—ATPase (SERCA); (2) sarcolemmal Na+−Ca2+ exchange (NCX); (3) sarcolemmal Ca2+-ATPase; and (4) mitochondrial Ca2+ uniport. For the myocyte to be in a steady state with respect to Ca2+ balance, the amount of Ca2+ extruded from the cell during relaxation must be the same as the amount of Ca2+ entry at each beat. Likewise, the amount of Ca2+ released from the SR must equal that reaccumulated by the action of the SERCA.
