Carotid body oxygen sensing.
The carotid body (CB) is a neural crest-derived organ whose major function is to sense changes in arterial oxygen tension to elicit hyperventilation in hypoxia. The CB is composed of clusters of neuron-like glomus, or type-I, cells enveloped by glia-like sustentacular, or type-II, cells. Responsiveness of CB to acute hypoxia relies on the inhibition of O(2)-sensitive K(+) channels in glomus cells, which leads to cell depolarisation, Ca(2+) entry and release of transmitters that activate afferent nerve fibres. Although this model of O(2) sensing is generally accepted, the molecular mechanisms underlying K(+) channel modulation by O(2) tension are unknown. Among the putative hypoxia-sensing mechanisms there are: the production of oxygen radicals, either in mitochondria or reduced nicotinamide adenine dinucleotide phosphate oxidases; metabolic mitochondrial inhibition and decrease of intracellular ATP; disruption of the prolylhydroxylase/hypoxia inducible factor pathway; or decrease of carbon monoxide production by haemoxygenase-2. In chronic hypoxia, the CB grows with increasing glomus cell number. The current authors have identified, in the CB, neural stem cells, which can differentiate into glomus cells. Cell fate experiments suggest that the CB progenitors are the glia-like sustentacular cells. The CB appears to be involved in the pathophysiology of several prevalent human diseases.
López-Barneo
J
J
Instituto de Biomedicina de Sevilla, Edificio de Laboratorios, Segunda planta, Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot s/n, 41013 Sevilla, Spain. lbarneo@us.es
Ortega-Sáenz
P
P
Pardal
R
R
Pascual
A
A
Piruat
J I
JI
D002248:Carbon Monoxide / Q000378:metabolism; D002344:Carotid Body / Q000378:metabolism / Q000502:physiology*; D019070:Cell Lineage; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D019255:NADPH Oxidases / Q000378:metabolism; D009432:Neural Crest / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D017382:Reactive Oxygen Species
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015221:Potassium Channels; D017382:Reactive Oxygen Species; D002248:Carbon Monoxide; D019255:NADPH Oxidases; D010100:Oxygen