Lidocaine blocks open and inactivated cardiac sodium channels

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Abstract
Guinea-pig papillary muscles were voltage-clamped using the single sucrose gap technique. The maximum upstroke velocity of the action potential (V max) was used as an indicator of the sodium conductance. Lidocaine (5 μmol/l to 40 μmol/l) reduced V max in a use-dependent fashion. Block of sodium channels developed during channel opening and while the channels were in-activated. 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.