AMP-activated protein kinase and the regulation of calcium signalling in oxygen-sensing cells

Anthony Mark Evans

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

All cells respond to metabolic stress. However, a variety of specialized cells, commonly referred to as O-2-sensing cells, are acutely sensitive to relatively small changes in P-O2. Within a variety of organisms such O-2-sensing cells have evolved as vital homeostatic mechanisms that monitor O-2 supply and alter respiratory and circulatory function, as well as the capacity of the blood to transport O-2. Thereby, arterial P-O2 may be maintained within physiological limits. In mammals, for example, two key tissues that contribute to this process are the pulmonary arteries and the carotid bodies. Constriction of pulmonary arteries by hypoxia optimizes ventilation-perfusion matching in the lung, whilst carotid body excitation by hypoxia initiates corrective changes in breathing patterns via increased sensory afferent discharge to the brain stem. Despite extensive investigation, the precise mechanism(s) by which hypoxia mediates these responses has remained elusive. It is clear, however, that hypoxia inhibits mitochondrial function in O-2-sensing cells over a range of PO2 that has no such effect on other cell types. This raised the possibility that AMP-activated protein kinase might function to couple mitochondrial oxidative phosphorylation to Ca2+ signalling mechanisms in O-2-sensing cells and thereby underpin pulmonary artery constriction and carotid body excitation by hypoxia. Our recent investigations have provided significant evidence in support of this view.

Original languageEnglish
Pages (from-to)113-123
Number of pages11
JournalThe Journal of Physiology
Volume574
DOIs
Publication statusPublished - 1 Jul 2006

Keywords

  • HYPOXIC PULMONARY VASOCONSTRICTION
  • CYCLIC ADP-RIBOSE
  • RAT CAROTID-BODY
  • SMOOTH-MUSCLE-CELLS
  • ARTERIAL CHEMORECEPTOR CELLS
  • MITOCHONDRIAL OXIDATIVE-PHOSPHORYLATION
  • KV-ALPHA SUBUNITS
  • I CELLS
  • K+ CHANNELS
  • INTRACELLULAR CA2+

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