Calcium sparks in smooth muscle

Abstract

Local intracellular Ca(2+) transients, termed Ca(2+) sparks, are caused by the coordinated opening of a cluster of ryanodine-sensitive Ca(2+) release channels in the sarcoplasmic reticulum of smooth muscle cells. Ca(2+) sparks are activated by Ca(2+) entry through dihydropyridine-sensitive voltage-dependent Ca(2+) channels, although the precise mechanisms of communication of Ca(2+) entry to Ca(2+) spark activation are not clear in smooth muscle. Ca(2+) sparks act as a positive-feedback element to increase smooth muscle contractility, directly by contributing to the global cytoplasmic Ca(2+) concentration ([Ca(2+)]) and indirectly by increasing Ca(2+) entry through membrane potential depolarization, caused by activation of Ca(2+) spark-activated Cl(-) channels. Ca(2+) sparks also have a profound negative-feedback effect on contractility by decreasing Ca(2+) entry through membrane potential hyperpolarization, caused by activation of large-conductance, Ca(2+)-sensitive K(+) channels. In this review, the roles of Ca(2+) sparks in positive- and negative-feedback regulation of smooth muscle function are explored. We also propose that frequency and amplitude modulation of Ca(2+) sparks by contractile and relaxant agents is an important mechanism to regulate smooth muscle function.