AJP - Cell Physiology, Vol 262, Issue 4 C882-C890, Copyright © 1992 by American Physiological Society
Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction
J. M. Post, J. R. Hume, S. L. Archer and E. K. Weir
Department of Physiology, University of Nevada School of Medicine, Reno 89557.
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.
