Document Detail

Central nervous system sodium channels are significantly suppressed at clinical concentrations of volatile anesthetics.
MedLine Citation:
PMID:  8624017     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Although voltage-dependent sodium channels have been proposed as possible molecular sites of anesthetic action, they generally are considered too insensitive to be likely molecular targets. However, most previous molecular studies have used peripheral sodium channels as models. To examine the interactions of volatile anesthetics with mammalian central nervous system voltage-gated sodium channels, rat brain IIA sodium channels were expressed in a stably transfected Chinese hamster ovary cell line, and their modification by volatile anesthetics was examined. METHODS: Sodium currents were measured using whole cell patch clamp recordings. Test solutions were equilibrated with the test anesthetics and perfused externally on the cells. Anesthetic concentrations in the perfusion solution were determined by gas chromatography. RESULTS: All anesthetics significantly suppressed sodium currents at clinical concentrations. This suppression occurred through at least two mechanisms: (1) a potential-independent suppression of resting or open sodium channels, and (2) a hyperpolarizing shift in the voltage-dependence of channel inactivation resulting in a potential-dependent suppression of sodium currents. The voltage-dependent interaction results in IC50 values for anesthetic suppression of sodium channels that are close to clinical concentrations at potentials near the resting membrane potential.
B Rehberg; Y H Xiao; D S Duch
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Anesthesiology     Volume:  84     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  1996 May 
Date Detail:
Created Date:  1996-06-14     Completed Date:  1996-06-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1223-33; discussion 27A     Citation Subset:  AIM; IM    
Department of Anesthesiology, Cornell University Medical College, New York, New York 10021, USA.
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MeSH Terms
Anesthetics, Inhalation / pharmacology*
Brain / drug effects*
CHO Cells
Dose-Response Relationship, Drug
Sodium Channels / drug effects*
Grant Support
Reg. No./Substance:
0/Anesthetics, Inhalation; 0/Sodium Channels

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