Wilson, David F., Arijit Roy, and Sukhamay Lahiri. Immediate and long-term responses of the
carotid body to high altitude. High Alt Med Biol 6:97–111, 2005.—High altitude and the decreased
environmental oxygen pressure have both immediate and chronic effects on the carotid body.
An immediate effect is to limit the oxygen available for mitochondrial oxidative phosphorylation,
and this leads to increased activity on the afferent nerves leading to the brain. In the isolated
carotid body preparation, the afferent nerve activity depends on the ratio of carbon monoxide
(CO), an inhibitor of respiratory chain function, to oxygen. The CO-induced increase in
afferent neural activity is reversed by light, and the wavelength dependence of this reversal
shows that the site of CO (and therefore oxygen) interaction is cytochrome a3 of the mitochondrial
respiratory chain. Thus, primary sensing of ambient oxygen pressure is through the oxygen
dependence of mitochondrial oxidative phosphorylation. The conductance of ion channels
in the cellular membranes may also be sensitive to oxygen pressure and, through this, modulate
the sensitivity to oxygen pressure. Longer-term exposure to high altitude results in progressive
changes in the carotid body that involve several mechanisms, including cellular energy
metabolism and hypoxia inducible factor-1α (HIF-1α). These changes begin within minutes of
exposure, but progress such that chronic exposure results in morphological and biochemical alterations
in the carotid body, including enlarged cells, increased catecholamine levels, altered
cellular appearance, and others. In the chronically adapted carotid body, responses to acute
changes in oxygen pressure are enhanced. The adaptive changes due to chronic hypoxia are
largely reversed upon return to lower altitudes.
