Early detection of an O₂ deficit in the bloodstream of mammals is essential. Thus, highly specialised cells have evolved to monitor O₂ supply and regulate, for example, ventilation-perfusion matching in the lung and breathing patterns. Thereby arterial pO₂ is maintained within physiological limits. Two O₂-sensing systems incorporating such cells are: (A) the pulmonary arteries, in which detection of a fall in airway pO₂ by smooth muscle and endothelial cells leads to constriction in order to divert blood flow to oxygen rich areas of the lung; (B) the carotid bodies, in which detection of a fall in arterial pO₂ by type I cells precipitates excitation-secretion coupling and increased sensory afferent discharge along the carotid sinus nerve to elicit corrective changes in breathing patterns via the brain stem. One finding common to each cell type is that mitochondrial oxidative phosphorylation is inhibited over a range of pO₂ that is without effect on cell types that do not serve to monitor O₂ supply. That apart, the precise nature of the coupling mechanism(s) remains controversial. However, one consequence of a reduction in mitochondrial oxidative phosphorylation would be a rise in the cellular AMP/ATP ratio, which would in turn augment the AMP-activated protein kinase (AMPK) signalling cascade. Thus, we have proposed that AMPK may underpin hypoxia-response coupling in O₂-sensing cells. Our experimental findings provide strong support for this proposal (for review see Evans, 2006).

Evans, A.M. (2006). J. Physiol., 574, 113-123.