Intracellular calcium channels: Inositol-1,4,5-trisphosphate receptors

The inositol-1,4,5-trisphosphate receptors (InsP₃Rs) are the major intracellular Ca²⁺-release channels in cells. Activity of InsP₃Rs is essential for elementary and global Ca²⁺ events in the cell. There are three InsP₃Rs isoforms that are present in mammalian cells. In this review we will focus primarily on InsP₃R type 1. The InsP₃R1 is a predominant isoform in neurons and it is the most extensively studied isoform. Combination of biophysical and structural methods revealed key mechanisms of InsP₃R function and modulation. Cell biological and biochemical studies lead to identification of a large number of InsP₃R-binding proteins. InsP₃Rs are involved in the regulation of numerous physiological processes, including learning and memory, proliferation, differentiation, development and cell death. Malfunction of InsP₃R1 play a role in a number of neurodegenerative disorders and other disease states. InsP₃Rs represent a potentially valuable drug target for treatment of these disorders and for modulating activity of neurons and other cells. Future studies will provide better understanding of physiological functions of InsP₃Rs in health and disease.