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Inositol trisphosphate receptor Ca2+ release channels in neurological diseases

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Abstract

The modulation of cytoplasmic Ca2+ concentration by release from internal stores through the inositol trisphosphate receptor (InsP3R) Ca2+ release channel is a ubiquitous signaling system involved in the regulation of numerous processes. Because of its ubiquitous expression and roles in regulating diverse cell physiological processes, it is not surprising that the InsP3R has been implicated in a number of disease states. However, relatively few mutations in InsP3R genes have been identified to date. Here, I will discuss mutations in the type 1 InsP3R that have been discovered by analyses of human patients and mice with neurological disorders. In addition, I will highlight diseases caused by mutations in other genes, including Huntington’s and Alzheimer’s diseases and some spinocerebellar ataxias, where the mutant proteins have been found to exert strong influences on InsP3R function that may link InsP3R to disease pathogenesis.

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Acknowledgements

Acknowledgement is made to the donors of ADR, a program of the American Health Assistance Foundation (A2008-137 to J.K.F.) and the National Institutes of Health (MH059937 and GM056328) for support of this research.

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  1. Departments of Physiology and Cell and Developmental Biology, University of Pennsylvania School of Medicine, B39 Anatomy-Chemistry Bldg., 414 Guardian Dr., Philadelphia, PA, 19104, USA

    J. Kevin Foskett

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This article is published as part of the special issue on channelopathies

Editor: Bernd Nilius, M.D., Ph.D.

Guest Editor: Alex Verkhratsky, M.D., Ph.D.

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Foskett, J.K. Inositol trisphosphate receptor Ca2+ release channels in neurological diseases. Pflugers Arch - Eur J Physiol 460, 481–494 (2010). https://doi.org/10.1007/s00424-010-0826-0

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