The carotid body oxygen sensor

• Published in: Current opinion in neurobiology Vol. 92; p. 103022
• Main Authors: Gao, Lin, Moreno-Domínguez, Alejandro, Ortega-Sáenz, Patricia, López-Barneo, José
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2025
• Subjects: Animals; Carotid Body - cytology; Carotid Body - metabolism; Carotid Body - physiology; Chemoreceptor Cells - metabolism; Chemoreceptor Cells - physiology; Humans; Oxygen - metabolism
• ISSN: 0959-4388; 1873-6882; 1873-6882
• DOI: 10.1016/j.conb.2025.103022

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. •Carotid body glomus cells are essential acute oxygen (O2)-sensing chemoreceptors.•Glomus cell acute O2-sensing depends on the constitutive expression of HIF2α.•HIF2α induces expression of atypical subunit isoforms in mitochondrial complex IV.•Mitochondrial complex I (MCI)-dependent production of nicotine adenine dinucleotide reduced form (NADH) and H2O2 in hypoxia modulates membrane ion channels.•The mitochondrial O2 sensor regulates cell’s excitability and transmitter release.