ACELL February 47/2

Jaggar, Jonathan H., Valerie A. Porter, W. Jonathan Lederer, and Mark T. Nelson. Calcium sparks in smooth muscle. Am. J. Physiol. Cell Physiol. 278: C235–C256, 2000.—Local intracellular Ca21 transients, termed Ca21 sparks, are caused by the coordinated opening of a cluster of ryanodine-sensitive Ca21 release channels in the sarcoplasmic reticulum of smooth muscle cells. Ca21 sparks are activated by Ca21 entry through dihydropyridine-sensitive voltage-dependent Ca21 channels, although the precise mechanisms of communication of Ca21 entry to Ca21 spark activation are not clear in smooth muscle. Ca21 sparks act as a positive-feedback element to increase smooth muscle contractility, directly by contributing to the global cytoplasmic Ca21 concentration ([Ca21]) and indirectly by increasing Ca21 entry through membrane potential depolarization, caused by activation of Ca21 spark-activated Cl2 channels. Ca21 sparks also have a profound negative-feedback effect on contractility by decreasing Ca21 entry through membrane potential hyperpolarization, caused by activation of large-conductance, Ca21sensitive K1 channels. In this review, the roles of Ca21 sparks in positiveand negative-feedback regulation of smooth muscle function are explored. We also propose that frequency and amplitude modulation of Ca21 sparks by contractile and relaxant agents is an important mechanism to regulate smooth muscle function.