Hypoxic pulmonary vasoconstriction: Redox events in oxygen sensing

Gregory B. Waypa, Paul T. Schumacker*

*Corresponding author for this work

Research output: Contribution to journalReview article

134 Scopus citations

Abstract

Recently, the mitochondria have become the focus of attention as the site of O2 sensing underlying hypoxic pulmonary vasoconstriction (HPV). However, two disparate models have emerged to explain how mitochondria react to a decrease in Po2. One model proposes that a drop in Po2 decreases the rate of mitochondrial reactive oxygen species (ROS) generation, resulting in a decrease in oxidant stress and an accumulation of reducing equivalents. The resulting shift of the cytosol to a reduced state causes the inhibition of voltage-dependent potassium channels, membrane depolarization, and the influx of calcium through voltage-gated (L-type) calcium channels. A second and opposing model suggests that hypoxia triggers a paradoxical increase in a mitochondrial-induced ROS signal. The resulting shift of the cytosol to an oxidized state triggers the release of intracellular calcium stores, recruitment of calcium channels in the plasma membrane, and activation of contraction. This article summarizes the potential involvement of a mitochondria-induced ROS signal in these two very different models.

Original languageEnglish (US)
Pages (from-to)404-414
Number of pages11
JournalJournal of applied physiology
Volume98
Issue number1
DOIs
StatePublished - Jan 1 2005

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Keywords

  • Mitochondria
  • Oxidants
  • Reactive oxygen species
  • Redox signaling

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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