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Am J Physiol Lung Cell Mol Physiol (January 21, 2005). doi:10.1152/ajplung.00379.2004
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Submitted on October 8, 2004
Accepted on January 19, 2005

Chronic Hypoxia Inhibits Kv Channel Gene Expression in Rat Distal Pulmonary Artery

Jian Wang1*, Letitia Weigand1, Wenqian Wang1, J. T. Sylvester1, and Larissa A. Shimoda1

1 Department of Medicine, Johns Hopkins University, Baltimore, MD, USA

* To whom correspondence should be addressed. E-mail: jwang31{at}jhmi.edu.

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 weeks. Kv 1.1, Kv 1.2, Kv 1.4, Kv 1.5, Kv 1.6, Kv 2.1, Kv 3.1, Kv 4.3, and Kv 9.3 channel {alpha}subunits and Kv 1, Kv 2 and Kv 3 {beta}-subunits were expressed in rat dPAs. Exposure to chronic hypoxia decreased mRNA and protein levels of Kv 1.1, Kv 1.5, Kv1.6, Kv 2.1 and Kv 4.3 {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.




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