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Systemic local anesthetics have been shown to have clinical efficacy against myotonias and some forms of neuropathic pain, so we sought to develop an in vitro model to examine the cellular basis for these drugs' effects. In frog sciatic nerves, studied in vitro by the sucrose\u2010gap method, peptide \u03b1\u2010toxins from sea anemone (ATXII) or scorpion (LQIIa) venom, which inhibit Na<jats:sup>+<\/jats:sup>channel inactivation, induced repetitively firing compound action potentials (CAPs) superimposed on a plateau depolarization lasting several seconds. The initial spike of the CAP was unaffected, but the plateau and repetitive firing were strongly suppressed by 5\u201330 \u03bcM lidocaine. Lidocaine caused a rapid, concentration\u2010dependent decay of the plateau, quantitatively consistent with blockade of open Na<jats:sup>+<\/jats:sup>channels. Early and late repetitive firing were equally suppressed by lidocaine with IC50 = 10 \u03bcM. After washout of lidocaine and LQIIa, the plateau and repetitive firing remained for &gt; 1 h, showing that lidocaine had not caused dissociation of channel\u2010bound \u03b1\u2010toxin. These findings indicate that therapeutic concentrations of lidocaine can reverse the \u201cabnormal\u201d features of action potentials caused by non\u2010inactivating Na<jats:sup>+<\/jats:sup>channels without affecting the normal spike component. \u00a9 2001 John Wiley &amp; Sons, Inc. Muscle Nerve 24: 634\u2013647, 2001<\/jats:p>","DOI":"10.1002\/mus.1049","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T21:24:42Z","timestamp":1030310682000},"page":"634-647","source":"Crossref","is-referenced-by-count":15,"title":["Lidocaine selectively blocks abnormal impulses arising from noninactivating Na channels"],"prefix":"10.1002","volume":"24","author":[{"given":"Alla","family":"Khodorova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad","family":"Meissner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley","family":"Leeson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary 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