{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T15:45:37Z","timestamp":1772898337573,"version":"3.50.1"},"reference-count":0,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1996,7,1]]},"abstract":"<jats:p> Hypoxic chemoreception in the carotid body involves selective inhibition of K+ channels in type I cells. We have investigated whether cytochrome P-450 may act as an O2 sensor coupling hypoxia to K+ channel inhibition, by investigating the actions of P-450 inhibitors to modulate channel activity (recorded using patch-clamp techniques) in type I cells isolated from 8-to 12-day-old rat pups. The imidazole antimycotic P-450 inhibitors miconazole and clotrimazole (1-10 microM) inhibited the Ca(2+)-activated (KCa) and voltage-gated K+ (Kv) currents in isolated type I cells. Single-channel recordings indicated that the KCa channels could be inhibited directly by miconazole. Miconazole also irreversibly inhibited Ca2+ channel currents. By contrast, acute application of the suicide substrate P-450 inhibitor, 1-aminobenzotriazole (1-ABT; 3 mM) was without effect on K+ or Ca2+ currents. Hypoxia (16-23 mmHg) reversibly inhibited K+ currents and prevented the inhibitory actions of miconazole. Furthermore, the inhibitory actions of miconazole could be partially reversed by hypoxia. Pretreatment of cells for 60 min with 3 mM 1-ABT substantially reduced the inhibitory actions of hypoxia on K+ currents. Our results indicate that imidazole antimycotic P-450 inhibitors can directly and nonselectively inhibit ionic channels in type I cells but, more importantly, provide evidence to suggest that hypoxic inhibition of K+ currents in type I cells is mediated in part at least by cytochrome P-450. <\/jats:p>","DOI":"10.1152\/ajpcell.1996.271.1.c85","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T19:05:26Z","timestamp":1514142326000},"page":"C85-C92","source":"Crossref","is-referenced-by-count":42,"title":["Effects of cytochrome P-450 inhibitors on ionic currents in isolated rat type I carotid body cells"],"prefix":"10.1152","volume":"271","author":[{"given":"C. J.","family":"Hatton","sequence":"first","affiliation":[{"name":"Institute for Cardiovascular Research, Leeds University, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Peers","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular Research, Leeds University, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.1996.271.1.C85","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T19:37:15Z","timestamp":1718653035000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.1996.271.1.C85"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,7,1]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1996,7,1]]}},"alternative-id":["10.1152\/ajpcell.1996.271.1.C85"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.1996.271.1.c85","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,7,1]]}}}