{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:17:39Z","timestamp":1781108259353,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1984,3]]},"abstract":"<jats:p>A rapid-mixing photolabeling apparatus is developed to resolve the kinetics of association of the noncompetitive channel blocker [3H]chlorpromazine (CPZ) with the membrane-bound acetylcholine (AcCho) receptor from Torpedo marmorata and to photolabel its subunits in the 100-milli-seconds to seconds time range. Rapid mixing of AcCho and [3H]CPZ with the receptor followed by brief (less than 20 msec) UV irradiation results in the selective labeling of the four chains of the AcCho receptor, according to a rapid bimolecular association process close to diffusion-controlled. Rapid association is not observed with the competitive antagonists d-tubocurarine or flaxedil or the snake venom alpha-toxins. Its initial rate increases with agonist concentration, with maxima of 0.6 for carbamoylcholine and 0.2 for phenyltrimethylammonium taking 1 for AcCho, with apparent dissociation constants of 30 microM, 400 microM, and 300 microM for AcCho, carbamoylcholine, and phenyltrimethylammonium, respectively, and with sigmoid shape (Hill coefficients of 1.1-1.3). Under conditions in which the receptor \"desensitizes\" and the ionic channel closes (preincubation with AcCho), rapid [3H]CPZ association decreases in parallel. It is concluded that the agonist-dependent rapid association of [3H]CPZ takes place at the level of a site common to all five subunits, which lies within the ion channel and becomes accessible when the channel opens.<\/jats:p>","DOI":"10.1073\/pnas.81.6.1897","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T05:38:09Z","timestamp":1149053889000},"page":"1897-1901","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":54,"title":["Time-resolved photolabeling by the noncompetitive blocker chlorpromazine of the acetylcholine receptor in its transiently open and closed ion channel conformations."],"prefix":"10.1073","volume":"81","author":[{"given":"T","family":"Heidmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J P","family":"Changeux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1984,3]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.81.6.1897","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T11:53:46Z","timestamp":1649850826000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.81.6.1897"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1984,3]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1984,3]]}},"alternative-id":["10.1073\/pnas.81.6.1897"],"URL":"https:\/\/doi.org\/10.1073\/pnas.81.6.1897","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1984,3]]},"assertion":[{"value":"1984-03-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}