Fig. 1.

Ca²⁺ fluxes associated with excitation-contraction coupling in mammalian cardiac myocytes. During the action potential, Ca²⁺ influx via L-type Ca²⁺ channels (LTCC) triggers Ca²⁺ release from the sarcoplasmic reticulum (SR) by Ca²⁺ binding to the ryanodine receptors (RyR2) in the SR membrane. In addition to interacting with the myofilaments (MF), Ca²⁺ is removed from the cytosol mainly by the SR Ca²⁺-ATPase (SERCA2a), which is regulated by phospholamban (PLN), and by the electrogenic sarcolemmal Na⁺/Ca²⁺ exchanger (NCX1), which is driven by the Na⁺ electrochemical gradient across the membrane. This gradient is maintained by the Na⁺-K⁺-ATPase (NKA). Intracellular [Na⁺] may also be affected by the operation of the Na⁺-H⁺ exchanger (NHE).