Document Detail

Ion channel voltage sensors: structure, function, and pathophysiology.
MedLine Citation:
PMID:  20869590     Owner:  NLM     Status:  MEDLINE    
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.
William A Catterall
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Neuron     Volume:  67     ISSN:  1097-4199     ISO Abbreviation:  Neuron     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-27     Completed Date:  2010-10-15     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  8809320     Medline TA:  Neuron     Country:  United States    
Other Details:
Languages:  eng     Pagination:  915-28     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Department of Pharmacology, University of Washington, Seattle, WA 98195-7280, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Amino Acid Sequence
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
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
Reg. No./Substance:
0/Ion Channels

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Neural progenitor nuclei in motion.
Next Document:  SCA1-like disease in mice expressing wild-type ataxin-1 with a serine to aspartic acid replacement a...