Intracellular Ca2+ activates phospholipase C

Abstract

It is well established that a receptor-mediated mechanism, perhaps involving a guanine nucleotide binding protein, directly activates polyphosphoinositide-specific phospholipase C. Recent evidence indicates that in excitable tissues a rise in cytosolic Ca2+ can also activate the phospholipase C. The activation of phospholipase C by Ca2+ can be a direct effect rather than a result of the Ca2+-dependent release of neurotransmitters which activate phospholipase C through a receptor-mediated mechanism. Ca2+-activated phospholipase C may represent a positive feedback system for Ca2+: small increases in cytosolic Ca2+ induced by Ca2+ influx across the plasma membrane may result in higher cytosolic Ca2+ concentrations due to IP3-induced release of Ca2+ from intracellular stores. The activation of phospholipase C by Ca2+ may also provide a mechanism for diacylglycerol generation and protein kinase C activation following Ca2+ influx. Thus, the regulation of phospholipase C activity by Ca2+ may be physiologically important in regulating cytosolic Ca2+ and protein kinase C in excitable tissues.