AMP-activated protein kinase and the regulation of Ca2+ signalling in O2-sensing cells.
All cells respond to metabolic stress. However, a variety of specialized cells, commonly referred to as O2-sensing cells, are acutely sensitive to relatively small changes in PO2. Within a variety of organisms such O2-sensing cells have evolved as vital homeostatic mechanisms that monitor O2 supply and alter respiratory and circulatory function, as well as the capacity of the blood to transport O2. Thereby, arterial PO2 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 O2-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 O2-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.
Evans
A Mark
AM
Division of Biomedical Sciences, School of Biology, Bute Building, University of St Andrews, St Andrews, Fife KY16 9TS, UK. ame3@st-andrews.ac.uk
D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D010100:Oxygen / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*
D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D010100:Oxygen; D002118:Calcium