Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction

J. M. Post, J. R. Hume, S. L. Archer, Edward K Weir

Research output: Contribution to journalArticle

395 Citations (Scopus)

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 Ca2+-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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume262
Issue number4 31-4
StatePublished - May 27 1992

Fingerprint

Potassium Channels
Vasoconstriction
Lung
Pulmonary Artery
Smooth Muscle Myocytes
Canidae
Nisoldipine
4-Aminopyridine
Tetraethylammonium
Membranes
Venoms
Oxygen
Kidney
Pressure

Keywords

  • 4- aminopyridine
  • Leiurus quinquestriatus venom
  • hypoxia
  • potassium currents
  • pulmonary vasculature
  • tetraethylammonium

Cite this

Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction. / Post, J. M.; Hume, J. R.; Archer, S. L.; Weir, Edward K.

In: American Journal of Physiology - Cell Physiology, Vol. 262, No. 4 31-4, 27.05.1992.

Research output: Contribution to journalArticle

Post, J. M. ; Hume, J. R. ; Archer, S. L. ; Weir, Edward K. / Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction. In: American Journal of Physiology - Cell Physiology. 1992 ; Vol. 262, No. 4 31-4.
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