The long term goal of this project is to gain an understanding of the molecular basis of cardiac excitability, concentrating on molecular structure-function relationships of cardiac K+ channels. The hypotheses to be tested are that specific regions and even specific amino acid residues are implicated in activation and deactivation gating and rectification of cardiac K channels.
The specific aims to be investigated include: (1) test of whether or not an extracellular ring of positive charges in hKv1.5 is a molecular determinant of outward rectification, (2) test whether or not the sixth transmembrane domain (S6) comprises part of the activation gate, This information should advance our understanding of the molecular physiology and pharmacology of cardiac K channels and further help in correlating cloned subunits with membrane currents in native cardiac cells. Finally, the information gained will expand our knowledge of the function of this important class of K channels, which may ultimately result in improved understanding of the genesis of cardiac arrhythmias and the development of better antiarrhythmic agents.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL047599-05A1
Application #
2028677
Study Section
Pharmacology A Study Section (PHRA)
Project Start
1992-08-01
Project End
2001-11-30
Budget Start
1997-03-01
Budget End
1997-11-30
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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