Chronic hypoxia inhibits Kv channel gene expression in rat distal pulmonary artery.
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.
Wang
Jian
J
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. jwang31@jhmi.edu
Weigand
Letitia
L
Wang
Wenqian
W
Sylvester
J T
JT
Shimoda
Larissa A
LA
D000818:Animals; D002478:Cells, Cultured; D002908:Chronic Disease; D015870:Gene Expression; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010100:Oxygen / Q000008:administration & dosage; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D021122:Protein Subunits; D011651:Pulmonary Artery / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D012333:RNA, Messenger; D010100:Oxygen