Alterations in a redox oxygen sensing mechanism in chronic hypoxia

H. L. Reeve, E. Michelakis, D. P. Nelson, E. K. Weir, S. L. Archer

Research output: Contribution to journalArticlepeer-review

123 Scopus citations

Abstract

The mechanism of acute hypoxic pulmonary vasoconstriction (HPV) may involve the inhibition of several voltage-gated K+ channels in pulmonary artery smooth muscle cells. Changes in Po2 can either be sensed directly by the channel(s) or be transmitted to the channel via a redox-based effector mechanism. In control lungs, hypoxia and rotenone acutely decrease production of activated oxygen species, inhibit K+ channels, and cause constriction. Two-day and 3-wk chronic hypoxia (CH) resulted in a decrease in basal activated oxygen species levels, an increase in reduced glutathione, and loss of HPV and rotenone-induced constriction. In contrast, 4-aminopyridine- and KCl-mediated constrictions were preserved. After 3-wk CH, pulmonary arterial smooth muscle cell membrane potential was depolarized, K+ channel density was reduced, and acute hypoxic inhibition of whole cell K+ current was lost. In addition, Kv1.5 and Kv2.1 channel protein was decreased. These data suggest that chronic reduction of the cytosol occurs before changes in K+ channel expression. HPV may be attenuated in CH because of an impaired redox sensor.

Original languageEnglish (US)
Pages (from-to)2249-2256
Number of pages8
JournalJournal of applied physiology
Volume90
Issue number6
DOIs
StatePublished - Jun 2001

Keywords

  • Glutathione
  • K channels
  • Oxygen sensor

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