{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T23:08:43Z","timestamp":1789945723506,"version":"4.0.1"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"3","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1988,3,1]]},"abstract":"<jats:p>Charybdotoxin (CTX), a small, basic protein from scorpion venom, strongly inhibits the conduction of K ions through high-conductance, Ca2+-activated K+ channels. The interaction of CTX with Ca2+-activated K+ channels from rat skeletal muscle plasma membranes was studied by inserting single channels into uncharged planar phospholipid bilayers. CTX blocks K+ conduction by binding to the external side of the channel, with an apparent dissociation constant of approximately 10 nM at physiological ionic strength. The dwell-time distributions of both blocked and unblocked states are single-exponential. The toxin association rate varies linearly with the CTX concentration, and the dissociation rate is independent of it. CTX is competent to block both open and closed channels; the association rate is sevenfold faster for the open channel, while the dissociation rate is the same for both channel conformations. Membrane depolarization enhances the CTX dissociation rate e-fold\/28 mV; if the channel's open probability is maintained constant as voltage varies, then the toxin association rate is voltage independent. Increasing the external solution ionic strength from 20 to 300 mM (with K+, Na+, or arginine+) reduces the association rate by two orders of magnitude, with little effect on the dissociation rate. We conclude that CTX binding to the Ca2+-activated K+ channel is a bimolecular process, and that the CTX interaction senses both voltage and the channel's conformational state. We further propose that a region of fixed negative charge exists near the channel's CTX-binding site.<\/jats:p>","DOI":"10.1085\/jgp.91.3.317","type":"journal-article","created":{"date-parts":[[2004,5,13]],"date-time":"2004-05-13T23:48:59Z","timestamp":1084492139000},"page":"317-333","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":184,"title":["Charybdotoxin block of single Ca2+-activated K+ channels. Effects of channel gating, voltage, and ionic strength."],"prefix":"10.1085","volume":"91","author":[{"given":"C S","family":"Anderson","sequence":"first","affiliation":[{"name":"Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02254."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"MacKinnon","sequence":"additional","affiliation":[{"name":"Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02254."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Smith","sequence":"additional","affiliation":[{"name":"Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02254."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Miller","sequence":"additional","affiliation":[{"name":"Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02254."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1988,3,1]]},"container-title":["The Journal of general physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/91\/3\/317\/1813608\/317.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/91\/3\/317\/1813608\/317.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T12:25:50Z","timestamp":1690460750000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jgp\/article\/91\/3\/317\/27637\/Charybdotoxin-block-of-single-Ca2-activated-K"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1988,3,1]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1988,3,1]]}},"URL":"https:\/\/doi.org\/10.1085\/jgp.91.3.317","relation":{},"ISSN":["0022-1295","1540-7748"],"issn-type":[{"value":"0022-1295","type":"print"},{"value":"1540-7748","type":"electronic"}],"subject":[],"published":{"date-parts":[[1988,3,1]]}}}