title: Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction.
abstract: Cellular mechanisms responsible for hypoxic pulmonary vasoconstriction were investigated in pulmonary arterial cells, isolated perfused lung, and pulmonary artery rings. Three K+ channel antagonists, Leiurus quinquestriatus venom, tetraethylammonium, and 4-aminopyridine, mimicked the effects of hypoxia in isolated lung and arterial rings by increasing pulmonary artery pressure and tension and also inhibited whole cell K+ currents in isolated pulmonary arterial cells. Reduction of oxygen tension from normoxic to hypoxic levels directly inhibited K+ currents and caused membrane depolarization in isolated canine pulmonary arterial smooth muscle cells but not in canine renal arterial smooth muscle cells. Nisoldipine or high buffering of intracellular Ca2+ concentration with [1,2-bis(2)aminophenoxy] ethane-N,N,N',N'-tetraacetic acid prevented hypoxic inhibition of K+ current, suggesting that a Ca(2+)-sensitive K+ channel may be responsible for the hypoxic response. These results indicate that K+ channel inhibition may be a key event that links hypoxia to pulmonary vasoconstriction by causing membrane depolarization and subsequent Ca2+ entry.
authors.affiliation: Department of Physiology, University of Nevada School of Medicine, Reno 89557.
authors.forename: J M
authors.initials: JM
authors.lastname: Post
authors.forename: J R
authors.initials: JR
authors.lastname: Hume
authors.forename: S L
authors.initials: SL
authors.lastname: Archer
authors.forename: E K
authors.initials: EK
authors.lastname: Weir
mesh_terms: D000818:Animals; D001158:Arteries / Q000473:pathology / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002469:Cell Separation; D004594:Electrophysiology; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology*; D011188:Potassium / Q000037:antagonists & inhibitors / Q000502:physiology; D015221:Potassium Channels / Q000378:metabolism*; D011652:Pulmonary Circulation; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction
chemical_list: D015221:Potassium Channels; D011188:Potassium