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The inositol trisphosphate calcium channel is inactivated by inositol trisphosphate


ACTIVATION of intracellular Ca2+ channels by inositol 1,4,5-tris-phosphate (Ins(l,4,5)P3) represents the initial Ca2+ mobilization step in response to many extracellular signals1. Here we report that Ins(l,4,5)P3-induced channel activation in permeabilized hepatocytes is followed by a time-dependent inactivation, which is a direct consequence of ligand binding. The inactivation by Ins(l,4,5)P3 parallels the quantal character of channel opening, giving rise to a unique process of incremental inactivation whereby discrete channel populations are inhibited at each Ins(l,4,5)P3 dose. Ins(l,4,5)P3 can induce inactivation in the absence of stored Ca2+, but the inactivation rate is enhanced by increases of cytosolic Ca2+. The inhibitory effect of Ins(l,4,5)P3 can be reversed by Ins(l,4,5)P3 washout, or by chelation of cytosolic Ca2+. Thus, Ins(l,4,5)P3 and Ca2+ act as coinhibitors of the Ins(l,4,5)P3-sensitive Ca2+ channel. Inactivation is an inherent consequence of Ins(l,4,5)P3-induced channel opening which can terminate increases of cytosolic Ca2+.

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Hajnóczky, G., Thomas, A. The inositol trisphosphate calcium channel is inactivated by inositol trisphosphate. Nature 370, 474–477 (1994).

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