Hypoxia reduces potassium currents in cultured rat pulmonary but not mesenteric arterial myocytes

X. J. Yuan, W. F. Goldman, M. L. Tod, L. J. Rubin, M. P. Blaustein

Research output: Contribution to journalArticle

273 Scopus citations

Abstract

To explore possible mechanisms underlying hypoxia-induced pulmonary vasoconstriction, the effect of hypoxia on outward K+ current (I(out)) 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 Ca2+-free media with 10 mM ethylene glycol-bis(β- aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), virtually all of the I(out), including both the rapidly inactivating component (I(rt)) and the steady-state (noninactivating) component (I(ss)), 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 I(rt) and I(ss) in PA myocytes, but not in MA myocytes. The hypoxia-sensitive I(ss) 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 Ca2+-free PSS (0.1 mM EGTA) from -38.4 ± 1.3 to -26.1 ± 3.9 mV. The hypoxia-induced inhibition of I(out) in PA cells was accompanied by an apparent increase in inward Ca2+ current. Removal of extracellular Ca2+ and addition of 2 mM EGTA to the bath solution while maintaining a Ca2+-free intracellular solution with 10 mM EGTA in the pipette (to prevent Ca2+-activated K+ channels from opening) did not preclude the hypoxia- induced inhibition of I(out) in PA cells. These data indicate that hypoxia attenuates voltage-gated K+ channel activity in PA cells but not in MA cells. The mechanism by which hypoxia inhibits I(out) is not known, but might be related to inhibition of oxidative metabolism. This inhibition of I(out) depolarizes the PA cells. By secondarily opening voltage-gated Ca2+ channels and promoting Ca2+ entry, the block of these K+ channels might be responsible for initiating hypoxia-induced pulmonary vasoconstriction.

Original languageEnglish (US)
Pages (from-to)L116-L123
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume264
Issue number2 8-2
DOIs
StatePublished - 1993

Keywords

  • hypoxia
  • patch- clamp technique
  • potassium channel
  • pulmonary arterial smooth muscle cells

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Fingerprint Dive into the research topics of 'Hypoxia reduces potassium currents in cultured rat pulmonary but not mesenteric arterial myocytes'. Together they form a unique fingerprint.

  • Cite this