| Ion channel voltage sensors: structure, function, and pathophysiology. | |
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MedLine Citation:
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PMID: 20869590 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Voltage-gated ion channels generate electrical signals in species from bacteria to man. Their voltage-sensing modules are responsible for initiation of action potentials and graded membrane potential changes in response to synaptic input and other physiological stimuli. Extensive structure-function studies, structure determination, and molecular modeling are now converging on a sliding-helix mechanism for electromechanical coupling in which outward movement of gating charges in the S4 transmembrane segments catalyzed by sequential formation of ion pairs pulls the S4-S5 linker, bends the S6 segment, and opens the pore. Impairment of voltage-sensor function by mutations in Na+ channels contributes to several ion channelopathies, and gating pore current conducted by mutant voltage sensors in Na(V)1.4 channels is the primary pathophysiological mechanism in hypokalemic periodic paralysis. The emerging structural model for voltage sensor function opens the way to development of a new generation of ion-channel drugs that act on voltage sensors rather than blocking the pore. |
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Authors:
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William A Catterall |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: Neuron Volume: 67 ISSN: 1097-4199 ISO Abbreviation: Neuron Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-27 Completed Date: 2010-10-15 Revised Date: 2012-04-26 |
Medline Journal Info:
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Nlm Unique ID: 8809320 Medline TA: Neuron Country: United States |
Other Details:
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Languages: eng Pagination: 915-28 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Pharmacology, University of Washington, Seattle, WA 98195-7280, USA. wcatt@u.washington.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Humans Ion Channel Gating / physiology* Ion Channels / chemistry*, physiology* Membrane Potentials / physiology Models, Molecular Nervous System Diseases / physiopathology* Protein Structure, Tertiary / physiology Structure-Activity Relationship |
| Grant Support | |
ID/Acronym/Agency:
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R01 NS015751-28/NS/NINDS NIH HHS; R01 NS015751-30/NS/NINDS NIH HHS; R01 NS15751/NS/NINDS NIH HHS; U01 NS058039/NS/NINDS NIH HHS; U01 NS058039-04/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Ion Channels |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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