The role of NADPH oxidase in carotid body arterial chemoreceptors.
O(2)-sensing in the carotid body occurs in neuroectoderm-derived type I glomus cells where hypoxia elicits a complex chemotransduction cascade involving membrane depolarization, Ca(2+) entry and the release of excitatory neurotransmitters. Efforts to understand the exquisite O(2)-sensitivity of these cells currently focus on the coupling between local P(O2) and the open-closed state of K(+)-channels. Amongst multiple competing hypotheses is the notion that K(+)-channel activity is mediated by a phagocytic-like multisubunit enzyme, NADPH oxidase, which produces reactive oxygen species (ROS) in proportion to the prevailing P(O2). In O(2)-sensitive cells of lung neuroepithelial bodies (NEB), multiple studies confirm that ROS levels decrease in hypoxia, and that E(M) and K(+)-channel activity are indeed controlled by ROS produced by NADPH oxidase. However, recent studies in our laboratories suggest that ROS generated by a non-phagocyte isoform of the oxidase are important contributors to chemotransduction, but that their role in type I cells differs fundamentally from the mechanism utilized by NEB chemoreceptors. Data indicate that in response to hypoxia, NADPH oxidase activity is increased in type I cells, and further, that increased ROS levels generated in response to low-O(2) facilitate cell repolarization via specific subsets of K(+)-channels.
Dinger
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B
Department of Physiology, University of Utah, School of Medicine, Salt Lake City, UT, USA. b.dinger@utah.edu
He
L
L
Chen
J
J
Liu
X
X
Gonzalez
C
C
Obeso
A
A
Sanders
K
K
Hoidal
J
J
Stensaas
L
L
Fidone
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S
D000818:Animals; D001158:Arteries / Q000201:enzymology / Q000294:innervation; D002344:Carotid Body / Q000201:enzymology*; D002628:Chemoreceptor Cells / Q000201:enzymology*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D019255:NADPH Oxidases / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D015221:Potassium Channels; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases