Calcium-induced calcium release in smooth muscle: the case for loose coupling

This article reviews the key experiments demonstrating calcium-induced calcium release (CICR) in smooth muscle and contrasts the biophysical and molecular features of coupling between the sarcolemmal (L-type Ca²⁺ channel) and sarcoplasmic reticulum (ryanodine receptor) Ca²⁺ channels in smooth and cardiac muscle. Loose coupling refers to the coupling process in smooth muscle in which gating of ryanodine receptors is non-obligate and may occur with a variable delay following opening of the sarcolemmal Ca²⁺ channels. These features have been observed in the earliest studies of CICR in smooth muscle and are in marked contrast to cardiac CICR, where a close coupling between T-tubular and SR membranes results in tight coupling between the gating events. The relationship between this “loose coupling” and distinct subcellular release sites within smooth muscle cells, termed frequent discharge sites, is discussed.