{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:09:47Z","timestamp":1791194987150,"version":"4.1.0"},"reference-count":24,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5704","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2004,12,17]]},"abstract":"<jats:p>Modulation of calcium-sensitive potassium (BK) channels by oxygen is important in several mammalian tissues, and in the carotid body it is crucial to respiratory control. However, the identity of the oxygen sensor remains unknown. We demonstrate that hemoxygenase-2 (HO-2) is part of the BK channel complex and enhances channel activity in normoxia. Knockdown of HO-2 expression reduced channel activity, and carbon monoxide, a product of HO-2 activity, rescued this loss of function. Inhibition of BK channels by hypoxia was dependent on HO-2 expression and was augmented by HO-2 stimulation. Furthermore, carotid body cells demonstrated HO-2\u2013dependent hypoxic BK channel inhibition, which indicates that HO-2 is an oxygen sensor that controls channel activity during oxygen deprivation.<\/jats:p>","DOI":"10.1126\/science.1105010","type":"journal-article","created":{"date-parts":[[2004,11,4]],"date-time":"2004-11-04T20:34:18Z","timestamp":1099600458000},"page":"2093-2097","source":"Crossref","is-referenced-by-count":392,"title":["Hemoxygenase-2 Is an Oxygen Sensor for a Calcium-Sensitive Potassium Channel"],"prefix":"10.1126","volume":"306","author":[{"given":"Sandile E. 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blot analysis of wild-type and BK\u03b1\u03b2 cells."},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(99)00019-5"},{"key":"e_1_3_1_18_2","unstructured":"Application of 30 \u03bcM of CO donor did not activate channels in wild-type cells."},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02003"},{"key":"e_1_3_1_20_2","unstructured":"Heme (1 nM) did not activate BK\u03b1\u03b2 channels; n = 8 patches; P > 0.25."},{"key":"e_1_3_1_21_2","unstructured":"CO donor (30 \u03bcM) increased NPo by a factor of 25 in membrane patches from carotid body glomus cells; n = 7 patches."},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.37.1.517"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7678352"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.6.1994"},{"key":"e_1_3_1_25_2","unstructured":"We thank J. Keen and A. Ashcroft for technical and scientific input into the 2D and spectroscopic analyses; S. Bourke S. Calaghan and T. Batten for microscopy; J. Kennedy for advice on inorganic syntheses; and M. Ashford for providing the BK\u03b1\u03b2 HEK293 cells. S.E.J.W. held a Commonwealth Scholarship. Funded by British Heart Foundation and Wellcome Trust."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1105010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T23:20:44Z","timestamp":1704842444000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1105010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,12,17]]},"references-count":24,"journal-issue":{"issue":"5704","published-print":{"date-parts":[[2004,12,17]]}},"alternative-id":["10.1126\/science.1105010"],"URL":"https:\/\/doi.org\/10.1126\/science.1105010","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1022130.263723","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1022130.250707","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1022130.254626","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,12,17]]}}}