The carotid body oxygen sensor.

Carotid body (CB) chemoreceptor glomus cells sense hypoxia through the inhibition of plasmalemmal K+ channels, which leads to the opening of Ca2+ channels, Ca2+ influx, and neurotransmitter release. The mechanism of O2 sensing and the regulation of membrane ion channels by O2 have remained undefined and a subject of debate. Here, we summarize the molecular pathway that underlies acute O2 sensing in the CB. This process does not rely on a single-molecule O2 sensor expressed in glomus cells but rather on HIF2α-dependent genetically specialized mitochondria that can detect changes in O2 tension, within physiological ranges, and generate biochemical signals that regulate membrane ion channels. The acute O2-sensing pathway in glomus cells could provide new targets for respiratory and cardiovascular pharmacology.