Journal
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Volume 281, Issue 1, Pages L202-L208Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.2001.281.1.L202
Keywords
pulmonary hypertension; voltage-gated potassium current; membrane potential; hypoxia-inducible factor-1; pulmonary arterial smooth muscle cell
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Funding
- NHLBI NIH HHS [HL-55338, T32-HL-07534, HL-51912] Funding Source: Medline
- NIDDK NIH HHS [DK-39869] Funding Source: Medline
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Chronic hypoxia depolarizes and reduces K(+) current in pulmonary arte rial smooth muscle cells (PASMCs). Our laboratory previously demonstrated that hypoxia-inducible factor-1 (HIF-1) contributed to the development of hypoxic pulmonary hypertension. In this study, electrophysiological parameters were measured in PASMCs isolated from intrapulmonary arteries of mice with one null allele at the Hif1a locus encoding HIF-1 alpha [Hif1a(+/-)] and from their wild-type [Hif1a(+/+)] littermates after 3 wk in air or 10% O(2). Hematocrit and right ventricular wall and left ventricle plus septum weights were measured. Capacitance, K(+) current, and membrane potential were measured with whole cell patch clamp. Similar to our laboratory's previous results, hypoxia-induced right ventricular hypertrophy and polycythemia were blunted in Hif1a(+/-) mice. Hypoxia increased PASMC capacitance in Hif1a(+/+) mice but not in Hif1a(+/-) mice. Chronic hypoxia depolarized and reduced K(+) current density in PASMCs from Hif1a(+/+) mice. In PASMCs from hypoxic Hif1a(+/-) mice, no reduction in K(+) current density was observed, and depolarization was significantly blunted. Thus partial deficiency of HIF-1 alpha is sufficient to impair hypoxia-induced depolarization, reduction of K(+) current density, and PASMC hypertrophy.
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