Lidocaine blocks open and inactivated cardiac sodium channels.
Guinea-pig papillary muscles were voltage-clamped using the single sucrose gap technique. The maximum upstroke velocity of the action potential (Vmax) was used as an indicator of the sodium conductance. Lidocaine (5 mumol/l to 40 mumol/l) reduced Vmax in a use-dependent fashion. Block of sodium channels developed during channel opening and while the channels were inactivated. Block of inactivated channels was not voltage-dependent over the -40 mV to +40 mV range. Recovery from block occurs upon repolarization, and for a given diastolic interval the recovery is more complete as the membrane potential is hyperpolarized over the -80 mV to -150 mV range. These results can be accounted for in terms of the modulated receptor hypothesis, where lidocaine has a low affinity for rested sodium channels, but a high affinity for open and inactivated channels.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008012:Lidocaine / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008955:Models, Cardiovascular; D012964:Sodium / Q000378:metabolism*
D007473:Ion Channels; D008012:Lidocaine; D012964:Sodium