| NADPH oxidase is an O2 sensor in airway chemoreceptors: evidence from K+ current modulation in wild-type and oxidase-deficient mice. | |
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MedLine Citation:
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PMID: 10760304 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Pulmonary neuroepithelial bodies (NEBs) are presumed airway chemoreceptors that express the putative O(2) sensor protein NADPH oxidase and O(2)-sensitive K(+) channels K(+)(O(2)). Although there is a consensus that redox modulation of K(+)(O(2)) may be a common O(2)-sensing mechanism, the identity of the O(2) sensor and related coupling pathways are still controversial. To test whether NADPH oxidase is the O(2) sensor in NEB cells, we performed patch-clamp experiments on intact NEBs identified by neutral red staining in fresh lung slices from wild-type (WT) and oxidase-deficient (OD) mice. In OD mice, cytochrome b(558) and oxidase function was disrupted in the gp91(phox) subunit coding region by insertion of a neomycin phosphotransferase (neo) gene. Expression in NEB cells of neo mRNA, a marker for nonfunctional gp91(phox), was confirmed by nonisotopic in situ hybridization. In WT cells, hypoxia (pO(2) = 15-20 mmHg; 1 mmHg = 133 Pa) caused a reversible inhibition ( approximately 46%) of both Ca(2+)-independent and Ca(2+)-dependent K(+) currents. In contrast, hypoxia had no effect on K(+) current in OD cells, even though both K(+) current components were expressed. Diphenylene iodonium (1 microM), an inhibitor of the oxidase, reduced K(+) current by approximately 30% in WT cells but had no effect in OD cells. Hydrogen peroxide (H(2)O(2); 0.25 mM), a reactive oxygen species generated by functional NADPH oxidase, augmented K(+) current by >30% in both WT and OD cells; further, in WT cells, H(2)O(2) restored K(+) current amplitude in the presence of diphenylene iodonium. We conclude that NADPH oxidase acts as the O(2) sensor in pulmonary airway chemoreceptors. |
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Authors:
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X W Fu; D Wang; C A Nurse; M C Dinauer; E Cutz |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 97 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2000 Apr |
Date Detail:
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Created Date: 2000-05-17 Completed Date: 2000-05-17 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 4374-9 Citation Subset: IM |
Affiliation:
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Division of Pathology, Department of Pediatric Laboratory Medicine, The Research Institute, The Hospital for Sick Children and University of Toronto, 555 University Avenue, Toronto, ON M5G 1X8, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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4-Aminopyridine
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pharmacology Animals Base Sequence Cell Hypoxia Chemoreceptor Cells / metabolism* DNA Primers Granulomatous Disease, Chronic / enzymology, genetics Lung / metabolism Membrane Glycoproteins / genetics Mice Mice, Knockout NADPH Oxidase / genetics, metabolism* Oxygen / metabolism* Potassium Channels / drug effects, metabolism* Tetraethylammonium Compounds / pharmacology Trachea / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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HL 52565/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CYBB protein, human; 0/DNA Primers; 0/Membrane Glycoproteins; 0/Potassium Channels; 0/Tetraethylammonium Compounds; 504-24-5/4-Aminopyridine; 7782-44-7/Oxygen; EC 1.6.3.1/NADPH Oxidase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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