Figure 3.

Cardiac excitation–contraction coupling. Membrane depolarization is initiated by opening of the Na⁺ channel (not shown) with Na⁺ entry. Extracellular Ca²⁺ enters via L‐type Ca²⁺ channel (I_Ca) and Na⁺/Ca²⁺ exchanger (NCX1), causing Ca²⁺ release from the ryanodine receptor (RyR) in the sarcoplasmic reticulum (SR). Ca²⁺ binds to troponin and initiates myofilament contraction. During diastole, Ca²⁺ is pumped back to the SR by SR Ca²⁺‐ATPase (SERCA) under the control of phospholamban (PLB). A small amount of Ca²⁺ is also taken up by the mitochondrial Ca²⁺ uniporter. The amount of Ca²⁺ that has entered during systole is extruded by Na⁺/Ca²⁺ exchanger and to a lesser extent by sarcolemmal Ca²⁺‐ATPase. Na⁺ that has entered via Na⁺ channel and Na⁺/Ca²⁺ exchanger is pumped out by Na⁺‐K⁺‐ATPase. Repolarization is mediated by opening of K⁺ channels (only the transient outward K⁺ current I_to responsible for early repolarization is shown). Phospholemman (PLM) associates with and is an endogenous regulator of Na⁺/Ca²⁺ exchanger, Na⁺‐K⁺‐ATPase, and possibly L‐type Ca²⁺ channel. Na⁺/Ca²⁺ exchanger is depicted as operating in the forward mode (Ca²⁺ efflux) in the sarcolemma and reverse mode (Ca²⁺ influx) in the t‐tubules. Broken arrows point to ion transporters, ion channels, and myofilaments that are altered after myocardial infarction.