{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T14:45:08Z","timestamp":1772894708306,"version":"3.50.1"},"reference-count":49,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1998,8,1]]},"abstract":"<jats:p> We examined the ability of local anesthetics to correct altered inactivation properties of rat skeletal muscle Na<jats:sup>+<\/jats:sup>channels containing the equine hyperkalemic periodic paralysis (eqHPP) mutation when expressed in Xenopusoocytes. Increased time constants of current decay in eqHPP channels compared with wild-type channels were restored by 1 mM benzocaine but were not altered by lidocaine or mexiletine. Inactivation curves, which were determined by measuring the dependence of the relative peak current amplitude after depolarization to \u221210 mV on conditioning prepulse voltages, could be shifted in eqHPP channels back toward that observed for wild-type (WT) channels using selected concentrations of benzocaine, lidocaine, and mexiletine. Recovery from inactivation at \u221280 mV (50-ms conditioning pulse) in eqHPP channels followed a monoexponential time course and was markedly accelerated compared with wild-type channels (\u03c4<jats:sub>WT<\/jats:sub>= 10.8 \u00b1 0.9 ms; \u03c4<jats:sub>eqHPP<\/jats:sub>= 2.9 \u00b1 0.4 ms). Benzocaine slowed the time course of recovery (\u03c4<jats:sub>eqHPP,ben<\/jats:sub> = 9.6 \u00b1 0.4 ms at 1 mM) in a concentration-dependent manner. In contrast, the recovery from inactivation with lidocaine and mexiletine had a fast component (\u03c4<jats:sub>fast,lid<\/jats:sub> = 3.2 \u00b1 0.2 ms; \u03c4<jats:sub>fast,mex<\/jats:sub> = 3.1 \u00b1 0.2 ms), which was identical to the recovery in eqHPP channels without drug, and a slow component (\u03c4<jats:sub>slow,lid<\/jats:sub> = 1,688 \u00b1 180 ms; \u03c4<jats:sub>slow,mex<\/jats:sub> = 2,323 \u00b1 328 ms). The time constant of the slow component of the recovery from inactivation was independent of the drug concentration, whereas the fraction of current recovering slowly depended on drug concentrations and conditioning pulse durations. Our results show that local anesthetics are generally incapable of fully restoring normal WT behavior in inactivation-deficient eqHPP channels. <\/jats:p>","DOI":"10.1152\/ajpcell.1998.275.2.c389","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T17:49:58Z","timestamp":1514137798000},"page":"C389-C400","source":"Crossref","is-referenced-by-count":27,"title":["Effects of local anesthetics on Na<sup>+<\/sup> channels containing  the equine hyperkalemic periodic paralysis mutation"],"prefix":"10.1152","volume":"275","author":[{"given":"Rajan L.","family":"Sah","sequence":"first","affiliation":[{"name":"Departments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada M5G 1L7"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert G.","family":"Tsushima","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada M5G 1L7"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter H.","family":"Backx","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada M5G 1L7"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.79.1.103"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.62.4.375"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119116"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.107.5.643"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.81.5.613"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.77.3.584"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/376683a0"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199004000-00022"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(91)90064-7"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(93)81045-2"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1995.73.5.1892"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/BF00374974"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90321-H"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90271-2"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.63.5.869"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90168-Q"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/BF00170658"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021684"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(96)79504-8"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.53.3.298"},{"key":"B22","first-page":"447","volume":"14","author":"Grant A. 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