ION CHANNELS AND PULMONARY VASCULAR TONE

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DESCRIPTION (Adapted from the Applicant's Abstract): 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.