{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T09:21:27Z","timestamp":1789809687805,"version":"4.0.1"},"reference-count":58,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2013,6,12]],"date-time":"2013-06-12T00:00:00Z","timestamp":1370995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2013,7,15]]},"abstract":"<jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Arterial chemoreceptors measure blood oxygen and are involved in the control of both breathing and the cardiovascular system.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Oxygen is mostly used by cells in their mitochondria to generate energy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In this study we have investigated the effects of oxygen starvation (hypoxia) on the mitochondria of specialised oxygen sensing cells from arterial chemoreceptors.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our data confirm that the mitochondria of these oxygen sensing cells are unusually sensitive to modest hypoxia. This effect seems to stem from a reduced affinity of the oxygen utilising enzyme cytochrome oxidase for oxygen.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results are consistent with a functional adaptation of the mitochondria of oxygen sensing cells that may enable them to play a direct role in the oxygen sensing process itself.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><jats:p><jats:bold>Abstract\u2002<\/jats:bold> The mechanism of oxygen sensing in arterial chemoreceptors is unknown but has often been linked to mitochondrial function. A common criticism of this hypothesis is that mitochondrial function is insensitive to physiological levels of hypoxia. Here we investigate the effects of hypoxia (down to 0.5% O<jats:sub>2<\/jats:sub>) on mitochondrial function in neonatal rat type\u20101 cells. The oxygen sensitivity of mitochondrial [NADH] was assessed by monitoring autofluorescence and increased in hypoxia with a <jats:italic>P<\/jats:italic><jats:sub>50<\/jats:sub> of 15 mm Hg (1 mm Hg = 133.3 Pa) in normal Tyrode or 46 mm Hg in Ca<jats:sup>2+<\/jats:sup>\u2010free Tyrode. Hypoxia also depolarised mitochondrial membrane potential (\u03c8<jats:sub>m<\/jats:sub>, measured using rhodamine 123) with a <jats:italic>P<\/jats:italic><jats:sub>50<\/jats:sub> of 3.1, 3.3 and 2.8 mm Hg in normal Tyrode, Ca<jats:sup>2+<\/jats:sup>\u2010free Tyrode and Tyrode containing the Ca<jats:sup>2+<\/jats:sup> channel antagonist Ni<jats:sup>2+<\/jats:sup>, respectively. In the presence of oligomycin and low carbonyl cyanide 4\u2010(trifluoromethoxy) phenylhydrazone (FCCP; 75 n<jats:sc>m<\/jats:sc>) \u03c8<jats:sub>m<\/jats:sub> is maintained by electron transport working against an artificial proton leak. Under these conditions hypoxia depolarised \u03c8<jats:sub>m<\/jats:sub>\/inhibited electron transport with a <jats:italic>P<\/jats:italic><jats:sub>50<\/jats:sub> of 5.4 mm Hg. The effects of hypoxia upon cytochrome oxidase activity were investigated using rotenone, myxothiazol, antimycin A, oligomycin, ascorbate and the electron donor tetramethyl\u2010<jats:italic>p<\/jats:italic>\u2010phenylenediamine. Under these conditions \u03c8<jats:sub>m<\/jats:sub> is maintained by complex IV activity alone. Hypoxia inhibited cytochrome oxidase activity (depolarised \u03c8<jats:sub>m<\/jats:sub>) with a <jats:italic>P<\/jats:italic><jats:sub>50<\/jats:sub> of 2.6 mm Hg. In contrast hypoxia had little or no effect upon NADH (<jats:italic>P<\/jats:italic><jats:sub>50<\/jats:sub>= 0.3 mm Hg), electron transport or cytochrome oxidase activity in sympathetic neurons. In summary, type\u20101 cell mitochondria display extraordinary oxygen sensitivity commensurate with a role in oxygen sensing. The reasons for this highly unusual behaviour are as yet unexplained.<\/jats:p>","DOI":"10.1113\/jphysiol.2013.257741","type":"journal-article","created":{"date-parts":[[2013,5,14]],"date-time":"2013-05-14T03:53:30Z","timestamp":1368503610000},"page":"3549-3563","source":"Crossref","is-referenced-by-count":95,"title":["Oxygen sensitivity of mitochondrial function in rat arterial chemoreceptor cells"],"prefix":"10.1113","volume":"591","author":[{"given":"Keith J.","family":"Buckler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Turner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,6,12]]},"reference":[{"key":"e_1_2_6_2_1","author":"Anichkov S","year":"1963","journal-title":"Pharmacology of the Carotid Body Chemoreceptors"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.73.6.1100"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)01290-3"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1997.sp021890"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-012-1089-8"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.819ba.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00374499"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1994.sp020143"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.819ba.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00495.2007"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.04.110188.001103"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-008-9166-6"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00310.2006"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019114"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019115"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2728(86)90112-X"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-07-04007.1994"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.7.2927"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2728(98)00076-0"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80038-0"},{"key":"e_1_2_6_22_1","first-page":"54","article-title":"Sinus carotidien et reflexes respiratoires: sensibilite des sinus carotidiens aux substances chimiques. 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