Function of NADPH Oxidase and Signaling by Reactive Oxygen Species in Rat Carotid Body Type I Cells
O2-sensing in the carotid body occurs in neuroectoderm-derived type I glomus cells, where hypoxia elicits a complex chemotransduction cascade involving membrane depolarization, Ca2+ entry and the release of excitatory neurotransmitters. Efforts to understand the exquisite O2-sensitivity of these cells have focused primarily on the relationship between PO2 and the activity of K+-channels. An important hypothesis developed by Acker and his colleagues suggests that coupling between local PO2 and the open-closed state of K+- channels is mediated by reactive oxygen species (ROS) generated by a phagocytic-like multisubunit enzyme, NADPH oxidase (Nox)(1). According to this scheme, ROS production will occur in proportion to the prevailing PO2, and a subset of K+-channels which control the EM, should close as ROS levels decrease. In O2-sensitive cells contained in lung neuroepithelial bodies (NEB), experiments have confirmed that ROS levels decrease in hypoxia, and that EM and K+-channel activity are indeed controlled by ROS produced by an Nox isoform similar, if not identical to the enzyme expressed in phagocytic cells that use ROS as part of an extracellular killing mechanism activated in response to invading micro-organisms(8; 15).
KeywordsReactive Oxygen Species Production NADPH Oxidase Carotid Body Glomus Cell Benzenesulfonyl Fluoride
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