The inositol trisphosphate calcium channel is inactivated by inositol trisphosphate

György Hajnóczky, Andrew Thomas

Research output: Contribution to journalArticle

144 Scopus citations

Abstract

ACTIVATION of intracellular Ca2+ channels by inositol 1,4,5-tris-phosphate (Ins(l,4,5)P3) represents the initial Ca 2+ mobilization step in response to many extracellular signals 1. 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 Ca 2+, 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+.

Original languageEnglish (US)
Pages (from-to)474-477
Number of pages4
JournalNature
Volume370
Issue number6489
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

All Science Journal Classification (ASJC) codes

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