Calcium sparks act as both positive- and negative-feedback elements to regulate smooth muscle contractility, with their frequency and amplitude modulation serving as an important regulatory mechanism.
This review highlights the dual role of calcium sparks in providing both positive and negative feedback regulation of smooth muscle contractility.
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.
Jaggar et al. (Tue,) conducted a review in Smooth muscle function. Calcium sparks was evaluated. Calcium sparks act as both positive- and negative-feedback elements to regulate smooth muscle contractility, with their frequency and amplitude modulation serving as an important regulatory mechanism.