The InsP 3 receptor: its role in neuronal physiology and neurodegeneration

The InsP 3 receptor is a ligand‐gated channel that releases Ca 2+ from intracellular stores in a variety of cell types, including neurons. Genetic studies from vertebrate and invertebrate model systems suggest that coordinated rhythmic motor functions are most susceptible to changes in Ca 2+ release from the InsP 3 receptor. In many cases, the InsP 3 receptor interacts with other signaling mechanisms that control levels of cytosolic Ca 2+ , suggesting that the maintenance of Ca 2+ homeostasis in normal cells could be controlled by the activity of the InsP 3 R. In support of this idea, recent studies show that altered InsP 3 receptor activity can be partially responsible for Ca 2+ dyshomeostasis seen in many neurodegenerative conditions. These observations open new avenues for carrying out genetic and drug screens that target InsP 3 R function in neurodegenerative conditions. BioEssays 27:1035–1047, 2005. © 2005 Wiley Periodicals, Inc.