Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction.
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.
Post
J M
JM
Department of Physiology, University of Nevada School of Medicine, Reno 89557.
Hume
J R
JR
Archer
S L
SL
Weir
E K
EK
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
D015221:Potassium Channels; D011188:Potassium