Lidocaine selectively blocks abnormal impulses arising from noninactivating Na channels

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Abstract
Abnormal, repetitive impulse firing arising from incomplete inactivation of Na+channels may be involved in several diseases of muscle and nerve, including familial myotonias and neuropathic pain syndromes. 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‐gap method, peptide α‐toxins from sea anemone (ATXII) or scorpion (LQIIa) venom, which inhibit Na+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 5–30 μM lidocaine. Lidocaine caused a rapid, concentration‐dependent decay of the plateau, quantitatively consistent with blockade of open Na+channels. Early and late repetitive firing were equally suppressed by lidocaine with IC50 = 10 μM. After washout of lidocaine and LQIIa, the plateau and repetitive firing remained for > 1 h, showing that lidocaine had not caused dissociation of channel‐bound α‐toxin. These findings indicate that therapeutic concentrations of lidocaine can reverse the “abnormal” features of action potentials caused by non‐inactivating Na+channels without affecting the normal spike component. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 634–647, 2001

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