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PMID: 9336185 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Defective fast inactivation recovery and deactivation account for sodium channel myotonia in the I1160V mutant.

Biophysical journal ·Vol. 73 ·No. 4 ·1997-10-00 ·Pages 1896-903

Richmond JE, VanDeCarr D, Featherstone DE, George AL, Ruben PC

Abstract

The skeletal muscle sodium channel mutant I1160V cosegregates with a disease phenotype producing myotonic discharges (observed as muscle stiffness) that are worsened by elevated K+ levels but unaffected by cooling. The I1160V alpha-subunit was co-expressed with the beta1-subunit in Xenopus oocytes. An electrophysiological characterization was undertaken to examine the underlying biophysical characteristics imposed by this mutation. Two abnormalities were found. 1) The voltage dependence of steady-state fast inactivation was reduced in I1160V, which resulted in faster rates of closed-state fast inactivation onset and recovery in I1160V compared with wild-type channels. 2) The rates of deactivation were slower in I1160V than in wild-type channels. Using a computer-simulated model, the combination of both defects elicited myotonic runs under conditions of elevated K+, consistent with the observed phenotype of the mutant.

MeSH Terms
Animals Base Sequence Biophysical Phenomena Biophysics Computer Simulation DNA Primers/genetics Electrophysiology Female In Vitro Techniques Kinetics Membrane Potentials Models, Biological Mutagenesis, Site-Directed Myotonia/genetics,metabolism Oocytes/metabolism Point Mutation Rats Sodium Channel Blockers Sodium Channels/genetics,metabolism Xenopus laevis
Chemicals
DNA Primers Sodium Channel Blockers Sodium Channels
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Richmond J E
Department of Biology, University of Utah, Salt Lake City 84112, USA.
VanDeCarr D
Featherstone D E
George A L
Ruben P C
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Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
DOI
10.1016/S0006-3495(97)78220-1
Published
1997-10-00
Pages
1896-903
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1181090
Subset
IM
Grants
NINDS NIH HHS · NS29204 · United States
NINDS NIH HHS · NS32387 · United States
External Links
PubMed source DOI: 10.1016/S0006-3495(97)78220-1 PMC Full Text View journal details
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