Action of tocainide and mexiletine on the excitation threshold of myelinated nerves.
The antiarrhythmic drugs tocainide and mexiletine increase the excitation threshold and decrease the Na permeability (PNa) in nerves. Hodgkin-Huxley model calculations suggest that the PNa decrease is not sufficient to explain the threshold increase at low concentrations (less than 0.7 mM tocainide; less than 0.1 mM mexiletine). On the other hand, a drug action on the membrane surface potential would be consistent with results of recent experiments. To clarify this point electrophysiological experiments on single nerve fibres (Rana esculenta) were carried out. Changes of the threshold interval (difference between membrane and threshold potential; Vm-Vs) were measured and compared with the corresponding changes of Vm and Vs (Vs was measured by means of the transition voltage VTr). The quantitatively good agreement between changes of Vm-Vs and those of VTr suggests that at low concentrations tocainide and mexiletine decrease nerve excitability by acting mainly on the membrane surface charge. This possibility was supported by an independent electrophoresis experiment with myelin vesicles from the same nerve material.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004594:Electrophysiology; D066298:In Vitro Techniques; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008801:Mexiletine / Q000494:pharmacology*; D009186:Myelin Sheath / Q000187:drug effects / Q000502:physiology; D009412:Nerve Fibers / Q000187:drug effects* / Q000502:physiology; D011893:Rana esculenta; D012964:Sodium / Q000378:metabolism; D016677:Tocainide
D008801:Mexiletine; D016677:Tocainide; D008012:Lidocaine; D012964:Sodium