Lidocaine selectively blocks abnormal impulses arising from noninactivating Na channels

Muscle & Nerve
A KhodorovaG R Strichartz

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 alpha-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 microM 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 microM. After washout of lidocaine and LQIIa, the plateau and repetitive firing remained for > 1 h, showing that lidocaine had not caused dissociation of c...Continue Reading

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Citations

Mar 22, 2005·Journal of Neurology·Gunnar WasnerRalf Baron
Jun 27, 2007·Journal of Palliative Medicine·Gary McCleane
Jul 26, 2003·Journal of Clinical Neurophysiology : Official Publication of the American Electroencephalographic Society·William W Campbell, Mark E Landau
Sep 30, 2004·Science's STKE : Signal Transduction Knowledge Environment·Ru-Rong Ji, Gary Strichartz
Apr 25, 2006·The Journal of Pain : Official Journal of the American Pain Society·Ron AmirGary R Strichartz
Aug 6, 2004·Journal of Medicinal Chemistry·Bin ShaoRichard B Carter

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