Mechanistic and Functional Aspects of Oscillatory Calcium Signalling
Mobilization of calcium from intracellular stores and the extracellular medium to yield an increase in cytosolic free Ca2+ ([Ca2+]i) is one of the most common forms of signal transduction utilized by extracellular stimuli in the control of cell function. It is now clear that receptor-induced increases in [Ca2+]i are generated, in part, by an elevation in the level of the second messenger inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) which is produced by a phospholipase C (PLC)-mediated hydrolysis of phosphatidyl inositol 4,5-bisphosphate (Berridge and Irvine, 1984). Ins(1,4,5)P3 is released into the cytosol where it interacts with an intracellular receptor which functions as a release channel for lumenal Ca2+ (Berridge and Irvine, 1989; Joseph and Williamson, 1989). However, intracellular Ca2+ stores are not uniformly sensitive to Ins(1,4,5)P3, as demonstrated in permeabilized cell studies where Ins(1,4,5)P3 can only release a fraction (30–50%) of the calcium accumulated by non-mitochondrial stores (Berridge and Irvine, 1984; Williamson et al., 1985; Joseph and Williamson, 1989). There is some debate as to the intracellular location of the Ins(1,4,5)P3-sensitive Ca2+ store. In Purkinje cells antibodies to the receptor have revealed localized concentrations on the nuclear envelope and parts of the endoplasmic reticulum (E.R.) (Ross etal., 1989).
KeywordsInositol Trisphosphate Cytoplasmic Free Calcium Agonist Dose Wave Initiation Single Hepatocyte
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