Does AMP-activated Protein Kinase Couple Inhibition of Mitochondrial Oxidative Phosphorylation by Hypoxia to Pulmonary Artery Constriction?
Pulmonary arteries constricts in response to hypoxia and thereby aid ventilation-perfusion matching in the lung. Although O2-sensitive mechanisms independent of mitochondria may also play a role, it is generally accepted that relatively mild hypoxia inhibits mitochondrial oxidative phosphorylation and that this underpins, at least in part, cell activation2-6. Despite this consensus, the mechanism by which inhibition of mitochondrial oxidative phosphorylation couples to Ca2+-dependent vasoconstriction has remained elusive. To date, the field has focussed on the role of the cellular energy status (ATP), reduced redox couples and reactive oxygen species4,5 respectively, but investigation of these hypotheses has delivered conflicting data and failed to unite the field8.
KeywordsPulmonary Artery AMPK Activation Hypoxic Pulmonary Vasoconstriction Mitochondrial Oxidative Phosphorylation Pulmonary Arterial Smooth Muscle Cell
Unable to display preview. Download preview PDF.
- 4.Killilea DW, Hester R, Balczon R, Babal P, Gillespie MN. Free radical production in hypoxic pulmonary artery smooth muscle cells. Am. J. Physiol. 2000;279: L408–L412.Google Scholar
- 16.Evans AM 2004 Hypoxia cell metabolism and cADPR accumulation. In: Yuan X-J (ed) Hypoxic pulmonary vasoconstriction: cellular and molecular mechanisms. Kluwer Academic Publications, p 313–338.Google Scholar
- 17.Dipp M, Nye PCG, Evans AM. Hypoxic release of calcium from the sarcoplasmic reticulum of pulmonary artery smooth muscle. Am. J. Physiol. 2001;281: L318–L325.Google Scholar
- 18.Durante PE, Mustard KJ, Park SH, Winder WW, Hardie DG. Effects of endurance training on activity and expression of AMP-activated protein kinase isoforms in rat muscles. Am. J. Physiol. 2002;283: E 178–86.Google Scholar