Leaky "feet" and sudden death.

Abstract

Increases in intracellular Ca2+ are crucial signaling events in many cell types. The cardiac isoform of the (sarco)endoplasmic reticulum Ca2+ release channel or ryanodine receptor (RyR2) is an important component of this signaling pathway in a wide variety of both excitable (nerve, smooth muscle, and heart) and nonexcitable (parotid, pancreas, and adrenal medulla) cells and is a critical component of excitation-contraction coupling in the heart.1,2⇓ The absence of RyR2 in knockout mice leads to an early embryonic lethal phenotype because its function is essential for regulation of the intrinsic beating rate, and this early lethality has prevented studying its absence in other cell types.3 Unlike skeletal muscle, where excitation-contraction coupling is mediated through a mechanical coupling between its RyR isoform, RyR1, and the skeletal isoform of the sarcolemmal slow voltage-gated Ca2+ channel (dihydropyridine receptor, DHPR), in cardiac muscle, Ca2+ release through RyR2 is caused by the inward Ca2+ flux through the cardiac DHPR …