{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T03:38:20Z","timestamp":1773459500020,"version":"3.50.1"},"reference-count":51,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2005,12]]},"abstract":"<jats:p>Membrane potential in oxygen-sensitive type I cells in carotid body is controlled by diverse sets of voltage-dependent and -independent K<jats:sup>+<\/jats:sup>channels. Coupling of Po<jats:sub>2<\/jats:sub>to the open-closed state of channels may involve production of reactive oxygen species (ROS) by NADPH oxidase. One hypothesis suggests that ROS are produced in proportion to the prevailing Po<jats:sub>2<\/jats:sub>and a subset of K<jats:sup>+<\/jats:sup>channels closes as ROS levels decrease. We evaluated ROS levels in normal and p47<jats:sup>phox<\/jats:sup>gene-deleted [NADPH oxidase knockout (KO)] type I cells using the ROS-sensitive dye dihydroethidium (DHE). In normal cells, hypoxia elicited an increase in ROS, which was blocked by the specific NADPH oxidase inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF, 3 mM). KO type I cells did not respond to hypoxia, but the mitochondrial uncoupler azide (5 \u03bcM) elicited increased fluorescence in both normal and KO cells. Hypoxia had no effect on ROS production in sensory and sympathetic neurons. Methodological control experiments showed that stimulation of neutrophils with a cocktail containing the chemotactic peptide N-formyl-Met-Leu-Phe (1 \u03bcM), arachidonic acid (10 \u03bcM), and cytochalasin B (5 \u03bcg\/ml) elicited a rapid increase in DHE fluorescence. This response was blocked by the NADPH oxidase inhibitor diphenyleneiodonium (10 \u03bcM). KO neutrophils did not respond; however, azide (5 \u03bcM) elicited a rapid increase in fluorescence. Physiological studies in type I cells demonstrated that hypoxia evoked an enhanced depression of K<jats:sup>+<\/jats:sup>current and increased intracellular Ca<jats:sup>2+<\/jats:sup>levels in KO vs. normal cells. Moreover, AEBSF potentiated hypoxia-induced increases in intracellular Ca<jats:sup>2+<\/jats:sup>and enhanced the depression of K<jats:sup>+<\/jats:sup>current in low O<jats:sub>2<\/jats:sub>. Our findings suggest that local compartmental increases in oxidase activity and ROS production inhibit the activity of type I cells by facilitating K<jats:sup>+<\/jats:sup>channel activity in hypoxia.<\/jats:p>","DOI":"10.1152\/ajplung.00015.2005","type":"journal-article","created":{"date-parts":[[2005,11,9]],"date-time":"2005-11-09T20:33:50Z","timestamp":1131568430000},"page":"L916-L924","source":"Crossref","is-referenced-by-count":44,"title":["Effect of p47<sup><i>phox<\/i><\/sup>gene deletion on ROS production and oxygen sensing in mouse carotid body chemoreceptor cells"],"prefix":"10.1152","volume":"289","author":[{"given":"L.","family":"He","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Dinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Sanders","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Hoidal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Obeso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Stensaas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Fidone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(94)90043-4"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1838(92)90125-Z"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1038\/204793a0"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)01122-6"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1997.sp021890"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(99)00015-8"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.00135.x"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1989.67.4.1578"},{"key":"R9","unstructured":"Bunn HF, Gu J, Huang E, Park JW, and Zhu H.Erythropoietin: a model system for studying oxygen-dependent gene regulation.J Exp Biol201: 1197\u20131201, 1998."},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1996.tb01195.x"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.20.11715"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2000.88.5.1880"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(01)00449-8"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1042\/bj2720743"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1042\/bj2370111"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.20.13292"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(97)00085-6"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199908200-00032"},{"key":"R19","unstructured":"Fidone S, Dinger BG, and Gonzalez C.Mechanisms of carotid body chemoreception. 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