This is a proposal to examine the physiologic contributions of K channels in pulmonary vascular smooth towards their response to hypoxia. The central hypotheses are that both acute and chronic hypoxia inhibit K channels at a functional or transcriptional level, respectively. Inhibition of these channels results in Em (membrane potential) depolarization and opening of voltage gated Ca channels initiating hypoxic vasoconstriction.
The aims are: 1) characterize electrophysiological properties of K channels and determine the molecular basis of native IK(V) in pulmonary artery smooth muscle cells (PASMC); 2) identify Kv channel alpha subunits that determine whole cell IK(V) and regulate Em; 3) specify Kv channels that are sensitive to hypoxia and define the mechanism of hypoxic mediated inhibition; and 4) examine effects of chronic hypoxia on function and expression of Kv channels in PASMC.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL054043-07
Application #
6389457
Study Section
Lung Biology and Pathology Study Section (LBPA)
Program Officer
Garfinkel, Susan J
Project Start
1995-04-01
Project End
2004-03-31
Budget Start
2001-04-01
Budget End
2002-03-31
Support Year
7
Fiscal Year
2001
Total Cost
$303,750
Indirect Cost
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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