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Inositol Trisphosphate Receptor Ca²⁺ Release Channels

Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania

The inositol 1,4,5-trisphosphate (InsP₃) receptors (InsP₃Rs) are a family of Ca²⁺ release channels localized predominately in the endoplasmic reticulum of all cell types. They function to release Ca²⁺ into the cytoplasm in response to InsP₃ produced by diverse stimuli, generating complex local and global Ca²⁺ signals that regulate numerous cell physiological processes ranging from gene transcription to secretion to learning and memory. The InsP₃R is a calcium-selective cation channel whose gating is regulated not only by InsP₃, but by other ligands as well, in particular cytoplasmic Ca²⁺. Over the last decade, detailed quantitative studies of InsP₃R channel function and its regulation by ligands and interacting proteins have provided new insights into a remarkable richness of channel regulation and of the structural aspects that underlie signal transduction and permeation. Here, we focus on these developments and review and synthesize the literature regarding the structure and single-channel properties of the InsP₃R.

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