Document Detail


Determinants of nicotinic receptor gating in natural and unnatural side chain structures at the M2 9' position.
MedLine Citation:
PMID:  8982168     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A nonsense suppression method was employed to incorporate a total of four natural and six unnatural residues at the 9' position of the M2 region in the beta, gamma, and delta subunits of muscle nicotinic receptors. In 33 pairwise comparisons of functional properties as influenced by structural features including side chain length, branching, and substitution of oxygen for methylene carbons, it is concluded that increased polarity in the side chains at the 9' position consistently increases the sensitivity to acetylcholine. In addition, the stereochemistry of the side chain can have marked influences on the EC50, primarily because of changes in the single-channel open time. For the case of isoleucine versus allo-isoleucine in the delta subunit, these changes are themselves modified by mutations at the 9' position in other subunits. The data suggest an especially strong interaction between the beta and delta subunits in the pore region, leading in turn to a suggested arrangement of subunits within the pentamer.
Authors:
P C Kearney; H Zhang; W Zhong; D A Dougherty; H A Lester
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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:  Neuron     Volume:  17     ISSN:  0896-6273     ISO Abbreviation:  Neuron     Publication Date:  1996 Dec 
Date Detail:
Created Date:  1997-01-27     Completed Date:  1997-01-27     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8809320     Medline TA:  Neuron     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1221-9     Citation Subset:  IM    
Affiliation:
Division of Biology, California Institute of Technology, Pasadena 91125, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Female
Ion Channel Gating*
Ion Channels / metabolism*
Oocytes
Receptors, Nicotinic / chemistry*,  metabolism*
Stereoisomerism
Time Factors
Xenopus
Grant Support
ID/Acronym/Agency:
NS11756/NS/NINDS NIH HHS; NS34407/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Ion Channels; 0/Receptors, Nicotinic

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


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