NADPH oxidase does not account fully for O2-sensing in model airway chemoreceptor cells.
A key feature of O2 sensing by chemoreceptor tissues is the hypoxic inhibition of K+ channels. However, mechanisms coupling a fall of pO2 to channel closure differ between tissues: O2 regulation of K+ channels in chemoreceptive neuroepithelial bodies and their immortal counterparts, H146 cells, involves altered reactive oxygen species generation by NADPH oxidase. In contrast, this enzyme complex is not involved in O2 sensing by the carotid body and pulmonary vasculature. Here, we provide pharmacological evidence to support a role for NADPH oxidase in hypoxic inhibition of K+ currents in H146 cells. Two structurally unrelated NADPH oxidase inhibitors, diphenylene iodonium and phenylarsine oxide, suppressed hypoxic inhibition of K+ currents recorded using the patch-clamp technique. Most importantly, however, neither inhibitor fully blocked this response. Our findings provide the first evidence that multiple mechanisms may coexist within a specific cell type to account for hypoxic suppression of K+ channel activity.
O'Kelly
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School of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, United Kingdom.
Peers
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Kemp
P J
PJ
D001152:Arsenicals / Q000494:pharmacology; D015687:Cell Hypoxia; D002460:Cell Line; D002628:Chemoreceptor Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D019255:NADPH Oxidases / Q000378:metabolism*; D009861:Onium Compounds / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D001152:Arsenicals; D004791:Enzyme Inhibitors; D009861:Onium Compounds; D015221:Potassium Channels; D017382:Reactive Oxygen Species; C029341:oxophenylarsine; C007517:diphenyleneiodonium; D019255:NADPH Oxidases; D010100:Oxygen