Hypoxia reduces potassium currents in cultured rat pulmonary but not mesenteric arterial myocytes.
To explore possible mechanisms underlying hypoxia-induced pulmonary vasoconstriction, the effect of hypoxia on outward K+ current (Iout) was evaluated in primary cultured rat pulmonary (PA) and mesenteric (MA) arterial smooth muscle cells using the whole cell patch-clamp technique. When the cells were bathed in standard physiological salt solution and the patch pipettes contained Ca(2+)-free media with 10 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), virtually all of the Iout, including both the rapidly inactivating component (Irt) and the steady-state (noninactivating) component (Iss), was mediated by voltage-gated K+ channels. Reduction of O2 tension in the bath solution from 155 Torr to < 74 Torr with sodium dithionite reversibly inhibited both Irt and Iss in PA myocytes, but not in MA myocytes. The hypoxia-sensitive Iss was activated at about -50 mV; thus, some of the channels responsible for this current may be open at the resting membrane potential (-40 +/- 1 mV) of PA cells used in this study. Hypoxia also significantly depolarized PA cells bathed in PSS (1.8 mM Ca2+) from -40.7 +/- 1.3 to -24.0 +/- 2.4 mV, and PA cells bathed in Ca(2+)-free PSS (0.1 mM EGTA) from -38.4 +/- 1.3 to -26.1 +/- 3.9 mV. The hypoxia-induced inhibition of Iout in PA cells was accompanied by an apparent increase in inward Ca2+ current.(ABSTRACT TRUNCATED AT 250 WORDS)
Yuan
X J
XJ
Department of Physiology, University of Maryland School of Medicine, Baltimore 21201.
Goldman
W F
WF
Tod
M L
ML
Rubin
L J
LJ
Blaustein
M P
MP
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004594:Electrophysiology; D000860:Hypoxia / Q000503:physiopathology; D008564:Membrane Potentials; D008638:Mesenteric Arteries / Q000473:pathology / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology*; D011188:Potassium / Q000037:antagonists & inhibitors / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology*; D051381:Rats
D015221:Potassium Channels; D011188:Potassium; D002118:Calcium