The cardiac contraction cycle: is Ca~(2+) going local?

摘要

The myriad of intracellular signaling pathways involving in-tracellular Ca~(2+) means Ca~(2+) plays a role in everything from cellular metabolism to cell death. In heart muscle Ca~(2+) is primarily known for its role in cellular contraction. Regulation of cardiac muscle contractility is achieved through modulation of the spa-tiotemporal nature of intracellular Ca~(2+) signals, operating in areas of restricted diffusion or microdomains, close to Ca~(2+) release sites. This Viewpoint article briefly integrates experimental evidence in support of this concept. Excitation-contraction (E-C) coupling in cardiac muscle is the transduction mechanism linking the action potential to cell shortening that occurs in response to a transient rise in intracellular calcium (Ca~(2+)_i). Activation of the L-type Ca~(2+) current (I_(Ca,L)) triggers a larger release of Ca~(2+) from the sarcoplasmic reticulum (SR) store via Ca~(2+)-induced Ca~(2+) release (CICR) due to activation of the SR Ca~(2+) release channel, the ryanodine receptor (RyR2), on the SR membrane (2, 9, 10). This Ca~(2+) reaches the myofilaments, which results in contraction of the cell and the generation of force.