Action potentials transmit the information of excitable cells. Voltage-sensitive sodium channels play a major role in cell excitability. Our understanding of the means by which electrically excitable cells communicate information is enhanced with a molecular approach to the function of voltage-gated ion channels. Sodium channels provide the trigger for the upstroke of the action potential by opening in response to membrane depolarization; open channels permit sodium influx whereas closed or inactivated channels do not. Excitability is regulated by two forms of channel deactivation, or closure; channel availability is dependent on deactivation of inactivated channels, and sodium influx during the falling phase of the action potential depends on deactivation of open channels. The Groome laboratory is interested in determining the structural bases of deactivation and its relation to muscle fiber excitability. In this proposal, the investigator will test the hypothesis that positively charged residues in voltage-sensing S4 segments in domains III and IV of the hNaV1.4 channel interact with negatively charged residues in the inactivation linker between those same two domains to regulate deactivation gating. Site directed mutagenesis and patch clamp electrophysiology as complementary approaches described in this proposal will provide a diversity of research opportunities to undergraduate students interested in molecular biology and neurobiology. The inter-dependent projects described in this proposal will provide excellent preparation for junior and senior students for graduate school or careers in the medical profession. The experimental plan will draw heavily on the curricular strengths of the Biology Department and will support recently developed courses in the Biology curriculum.

Agency
National Science Foundation (NSF)
Institute
Division of Integrative Organismal Systems (IOS)
Type
Standard Grant (Standard)
Application #
0429565
Program Officer
Aixa Alfonso
Project Start
Project End
Budget Start
2004-04-01
Budget End
2008-03-31
Support Year
Fiscal Year
2004
Total Cost
$166,593
Indirect Cost
Name
Idaho State University
Department
Type
DUNS #
City
Pocatello
State
ID
Country
United States
Zip Code
83209