Abstract
The inositol 1,4,5-trisphosphate receptor (IP3 R) is a huge Ca2+ channel that is localized at the endoplasmic reticulum. The IP3 R releases Ca2+ from the endoplasmic reticulum upon binding to IP3 , which is produced by various extracellular stimuli through phospholipase C activation. All vertebrate organisms have three subtypes of IP3 R genes, which have distinct properties of IP3 -binding and Ca2+ sensitivity, and are differently regulated by phosphorylation and by their associated proteins. Each cell type expresses the three subtypes of IP3 R in a distinct proportion, which is important for creating and maintaining spatially and temporally appropriate intracellular Ca2+ level patterns for the regulation of specific physiological phenomena. Of the three types of IP3 Rs, the type 1 receptor (IP3 R1) is dominantly expressed in the brain and is important for brain function. Recent emerging evidence suggests that abnormal Ca2+ signals from the IP3 R1 are closely associated with human brain pathology. In this review, we focus on the recent advances in our knowledge of the regulation of IP3 R1 and its functional implication in human brain diseases, as revealed by IP3 R mutation studies and analysis of human disease-associated genes. This article is part of the mini review series "60th Anniversary of the Japanese Society for Neurochemistry".
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