{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T23:26:54Z","timestamp":1747783614776},"reference-count":0,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1992,1,1]]},"abstract":"<jats:p>Batrachotoxin (BTX)-modified Na+ currents were characterized in GH3 cells with a reversed Na+ gradient under whole-cell voltage clamp conditions. BTX shifts the threshold of Na+ channel activation by approximately 40 mV in the hyperpolarizing direction and nearly eliminates the declining phase of Na+ currents at all voltages, suggesting that Na+ channel inactivation is removed. Paradoxically, the steady-state inactivation (h infinity) of BTX-modified Na+ channels as determined by a two-pulse protocol shows that inactivation is still present and occurs maximally near -70 mV. About 45% of BTX-modified Na+ channels are inactivated at this voltage. The development of inactivation follows a sum of two exponential functions with tau d(fast) = 10 ms and tau d(slow) = 125 ms at -70 mV. Recovery from inactivation can be achieved after hyperpolarizing the membrane to voltages more negative than -120 mV. The time course of recovery is best described by a sum of two exponentials with tau r(fast) = 6.0 ms and tau r(slow) = 240 ms at -170 mV. After reaching a minimum at -70 mV, the h infinity curve of BTX-modified Na+ channels turns upward to reach a constant plateau value of approximately 0.9 at voltages above 0 mV. Evidently, the inactivated, BTX-modified Na+ channels can be forced open at more positive potentials. The reopening kinetics of the inactivated channels follows a single exponential with a time constant of 160 ms at +50 mV. Both chloramine-T (at 0.5 mM) and alpha-scorpion toxin (at 200 nM) diminish the inactivation of BTX-modified Na+ channels. In contrast, benzocaine at 1 mM drastically enhances the inactivation of BTX-modified Na+ channels. The h infinity curve reaches minimum of less than 0.1 at -70 mV, indicating that benzocaine binds preferentially with inactivated, BTX-modified Na+ channels. Together, these results imply that BTX-modified Na+ channels are governed by an inactivation process.<\/jats:p>","DOI":"10.1085\/jgp.99.1.1","type":"journal-article","created":{"date-parts":[[2004,5,13]],"date-time":"2004-05-13T23:48:59Z","timestamp":1084492139000},"page":"1-20","update-policy":"http:\/\/dx.doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Inactivation of batrachotoxin-modified Na+ channels in GH3 cells. Characterization and pharmacological modification."],"prefix":"10.1085","volume":"99","author":[{"given":"G K","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Anesthesia Research Laboratories, Harvard Medical School, Boston, Massachusetts."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S Y","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesia Research Laboratories, Harvard Medical School, Boston, Massachusetts."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1992,1,1]]},"container-title":["The Journal of general physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/99\/1\/1\/1814775\/1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/99\/1\/1\/1814775\/1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T12:38:03Z","timestamp":1690461483000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jgp\/article\/99\/1\/1\/27989\/Inactivation-of-batrachotoxin-modified-Na-channels"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,1,1]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1992,1,1]]}},"URL":"https:\/\/doi.org\/10.1085\/jgp.99.1.1","relation":{},"ISSN":["0022-1295","1540-7748"],"issn-type":[{"value":"0022-1295","type":"print"},{"value":"1540-7748","type":"electronic"}],"subject":[],"published":{"date-parts":[[1992,1,1]]}}}