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Am J Physiol Lung Cell Mol Physiol 288: L1049-L1058, 2005. First published January 21, 2005; doi:10.1152/ajplung.00379.2004
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Chronic hypoxia inhibits Kv channel gene expression in rat distal pulmonary artery

Jian Wang, Letitia Weigand, Wenqian Wang, J. T. Sylvester, and Larissa A. Shimoda

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland

Submitted 8 October 2004 ; accepted in final form 19 January 2005

In pulmonary arterial smooth muscle cells (PASMCs), voltage-gated K+ (Kv) channels play an important role in regulating membrane potential, cytoplasmic free Ca2+ concentration, and pulmonary vasomotor tone. Previous studies demonstrated that exposure of rats to chronic hypoxia decreased Kv channel function in PASMCs from distal pulmonary arteries (dPA). To determine whether this decrease in function was due to decreased expression of Kv channel proteins and which Kv proteins might be involved, we analyzed Kv channel gene expression in intact, endothelium-denuded dPAs obtained from rats exposed to 10% O2 for 3 wk. Kv1.1, Kv1.2, Kv1.4, Kv1.5, Kv1.6, Kv2.1, Kv3.1, Kv4.3, and Kv9.3 channel {alpha}-subunits and Kv1, Kv2, and Kv3 {beta}-subunits were expressed in rat dPAs. Exposure to chronic hypoxia decreased mRNA and protein levels of Kv1.1, Kv1.5, Kv1.6, Kv2.1, and Kv4.3 {alpha}-subunits in dPAs but did not alter gene or protein expression of these channels in aorta. Furthermore, chronic hypoxia did not alter the mRNA levels of {beta}-subunits in dPAs. These results suggest that diminished transcription of Kv {alpha}-subunits may reduce the number of functional Kv channels in dPAs during prolonged hypoxia, causing the decreased Kv current previously observed in PASMCs and leading to pulmonary artery vasoconstriction.

voltage-gate K+


Address for reprint requests and other correspondence: J. Wang, Division of Pulmonary and Critical Care Medicine, The Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, JHAAC 4A.52, Baltimore, MD 21224 (E-mail: jwang31{at}jhmi.edu)




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