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Gain of function mutants: Ion channels and G protein-coupled receptors

Lester, Henry A. and Karschin, Andreas (2000) Gain of function mutants: Ion channels and G protein-coupled receptors. Annual Review of Neuroscience, 23 . pp. 89-125. ISSN 0147-006X. https://resolver.caltech.edu/CaltechAUTHORS:LESarn00

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Abstract

Many ion channels and receptors display striking phenotypes for gain-of-function mutations but milder phenotypes for null mutations. Gain of molecular function can have several mechanistic bases: selectivity changes, gating changes including constitutive activation and slowed inactivation, elimination of a subunit that enhances inactivation, decreased drug sensitivity, changes in regulation or trafficking of the channel, or induction of apoptosis. Decreased firing frequency can occur via increased function of K+ or Cl- channels. Channel mutants also cause gain-of-function syndromes at the cellular and circuit level; of these syndromes, the cardiac long-QT syndromes are explained in a more straightforward way than are the epilepsies. G protein-coupled receptors are also affected by activating mutations.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1146/annurev.neuro.23.1.89DOIUNSPECIFIED
ORCID:
AuthorORCID
Lester, Henry A.0000-0002-5470-5255
Additional Information:"Reprinted, with permission, from the Annual Review of Neuroscience, Volume 23 copyright 2000 by Annual Reviews, www.annualreviews.org" We thank A Auerbach, NJM Birdsall, J Garcia-Anoveros, R Dingledine, AG Engel, F Lehmann-Horn, D Mackinnon, JL Noebels, RL Ruff, M Sanguinetti, W Shi, M Yuzaki, and our colleagues at Caltech and Gottingen for many comments. Preparation of this chapter was supported by the Alexander von Humboldt Foundation. Work in our laboratories on this topic is supported by National Institutes of Health grants GM29836, MH49176, and NS11756, by the California Tobacco-Related Disease Research Program, and by the Sidney Stern Foundation.
Funders:
Funding AgencyGrant Number
Alexander von Humboldt FoundationUNSPECIFIED
NIHGM29836
NIHMH49176
NIHNS11756
California Tobacco-Related Disease Research ProgramUNSPECIFIED
Sidney Stern FoundationUNSPECIFIED
Subject Keywords:EPILEPSY; NEURODEGENERATION; WEAVER; GENETIC DISEASE; LONG-QT SYNDROME; EPITHELIAL NA+ CHANNEL; KNOCKDOWN-RESISTANCE KDR; FRONTAL-LOBE EPILEPSY; INHERITED CARDIAC-ARRHYTHMIA; RECTIFYING K+ CHANNELS; GATED SODIUM-CHANNEL; CONSTITUTIVELY ACTIVATING MUTATION; COCKROACHES BLATTELLA-GERMANICA; NEMATODE CAENORHABDITIS-ELEGANS
Record Number:CaltechAUTHORS:LESarn00
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:LESarn00
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:1458
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:19 Jan 2006
Last Modified:02 Oct 2019 22:43

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