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Oxygen sensing by the carotid body: is it all just rotten eggs?

Kemp, Paul J. and Telezhkin, Vsevolod 2014. Oxygen sensing by the carotid body: is it all just rotten eggs? Antioxidants & Redox Signaling 20 (5) , pp. 794-804. 10.1089/ars.2013.5377

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Abstract

Significance: Ventilatory responses to hypoxia are initiated by the carotid body, where inhibition of specific K+ channels causes cell depolarization, voltage-gated Ca2+ influx, and neurotransmitter release. The identity of the upstream oxygen (O2) sensor is still controversial. Recent Advances: The activity of BKCa channels is regulated by O2, carbon monoxide (CO), and hydrogen sulfide (H2S), suggesting that integration of these signals may be crucial to the physiological response of this tissue. BKCa is colocalized with hemeoxygenase-2, an enzyme that generates CO in the presence of O2, and CO is a BKCa channel opener. Reduced CO during hypoxia results in channel closure, conferring a degree of O2 sensitivity to the BKCa channel. Conversely, H2S is a potent BKCa inhibitor. H2S is produced endogenously by cystathionine-β-synthase and cystathionine-γ-lyase in the rat carotid body, and its intracellular concentration is dependent upon the balance between its enzymatic generation and its mitochondrial breakdown. During hypoxia, mitochondrial oxidation of H2S in many tissues is reduced, leading to hypoxia-evoked rises in its concentration. This may be sufficient to inhibit K+ channels and lead to carotid body excitation. Critical Issues: Carotid body function is heavily dependent upon regulated production and breakdown of CO and H2S and integration of signals from these newly emerging gasotransmitters, in combination with several other proposed mechanisms, may refine, or even define, responses of this tissue to hypoxia. Future Directions: Since several other sensors have been postulated, the challenge of future research is to begin to integrate each in a unifying mechanism, as has been attempted for the first time herein.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > Q Science (General)
Publisher: Mary Ann Liebert
ISSN: 1523-0864
Last Modified: 31 Jan 2020 03:30
URI: http://orca-mwe.cf.ac.uk/id/eprint/58416

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