{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:39:50Z","timestamp":1790642390845,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["PRJ201502629"],"award-info":[{"award-number":["PRJ201502629"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>The carotid body (CB) is the main oxygen (O<jats:sub>2<\/jats:sub>) sensing organ that mediates reflex hyperventilation and increased cardiac output in response to hypoxaemia. Acute O<jats:sub>2<\/jats:sub> sensing is an intrinsic property of CB glomus cells, which contain special mitochondria to generate signalling molecules (NADH and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) that modulate membrane K<jats:sup>+<\/jats:sup> channels in response to lowered O<jats:sub>2<\/jats:sub> tension (hypoxia). In parallel with these membrane\u2010associated events, glomus cells are highly sensitive to mitochondrial electron transport chain (ETC) inhibitors. It was suggested that a decrease in oxidative production of ATP is a critical event mediating hypoxia\u2010induced cell depolarization. Here, we show that rotenone [an inhibitor of mitochondrial complex (MC) I] activates rat and mouse glomus cells but abolishes their responsiveness to hypoxia. Rotenone does not prevent further activation of the cells by cyanide (a blocker of MCIV) or glucose deprivation. Responsiveness to glucose deprivation is enhanced in O<jats:sub>2<\/jats:sub>\u2010insenstive glomus cells with genetic disruption of MCI. These findings suggest that acute O<jats:sub>2<\/jats:sub> sensing requires a functional MCI but that a decrease in intracellular ATP, presumably produced by the simultaneous inhibition of MCI and MCIV, is not involved in hypoxia signalling. In support of this concept, ATP levels in single glomus cells were unaltered by hypoxia, but rapidly declined following exposure of the cells to low glucose or to inhibitors of oxidative phosphorylation. These observations indicate that a reduction in intracellular ATP does not participate in physiological acute O<jats:sub>2<\/jats:sub> sensing. However, local decreases in ATP of glycolytic origin may contribute to low glucose signalling in glomus cells.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16558-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The carotid body contains oxygen\u2010sensitive glomus cells with specialized mitochondria that generate signalling molecules (NADH and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) to inhibit membrane K<jats:sup>+<\/jats:sup> channels in response to hypoxia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Glomus cells are highly sensitive to electron transport chain (ETC) blockers. It was suggested that a decrease in intracellular ATP is the main signal inducing K<jats:sup>+<\/jats:sup> channel inhibition and depolarization in response to hypoxia or ETC blockade.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Rotenone, an inhibitor of mitochondrial complex (MC) I, activates glomus cells but abolishes their responsiveness to hypoxia. However, rotenone does not prevent further activation of glomus cells by cyanide (an MCIV blocker) or glucose deprivation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Single\u2010cell ATP levels were unaltered by hypoxia, but decreased rapidly following exposure of glomus cells to 0\u00a0mM glucose or inhibitors of oxidative phosphorylation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>A reduction in intracellular ATP does not participate in signalling acute hypoxia. However, it may contribute to hypoglycaemia signalling in glomus cells.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp287130","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T13:29:11Z","timestamp":1739366951000},"page":"1091-1107","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Intracellular signalling in arterial chemoreceptors during acute hypoxia and glucose deprivation: role of ATP"],"prefix":"10.1113","volume":"603","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6569-0397","authenticated-orcid":false,"given":"Mar\u00eda","family":"Torres\u2010L\u00f3pez","sequence":"first","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS) Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla  Sevilla Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina Universidad 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