Calcium sparks in smooth muscle

1 Department of Pharmacology, College of Medicine, The University of Vermont, Burlington, Vermont 05405; and 2 Medical Biotechnology Center, University of Maryland Biotechnology Institute, and Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201 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. ryanodine-sensitive calcium-release channel; voltage-dependent calcium channel; calcium-sensitive potassium channel; calcium-activated chloride channel; sarcoplasmic reticulum