Interactions between quaternary lidocaine, the sodium channel gates, and tetrodotoxin.
A voltage clamp technique was used to study sodium currents and gating currents in squid axons internally perfused with the membrane impermeant sodium channel blocker, QX-314. Block by QX-314 is strongly and reversibly enhanced if a train of depolarizing pulses precedes the measurement. The depolarization-induced block is antagonized by external sodium. This antagonism provides evidence that the blocking site for the drug lies inside the channel. Depolarization-induced block of sodium current by QX-314 is accompanied by nearly twofold reduction in gating charge movement. This reduction does not add to a depolarization-induced immobilization of gating charge normally present and believed to be associated with inactivation of sodium channels. Failure to act additively suggests that both, inactivation and QX-314, affect the same component of gating charge movement. Judged from gating current measurement, a drug-blocked channel is an inactivated channel. In the presence of external tetrodotoxin and internal QX-314, gating charge movement is always half its normal size regardless of conditioning, as it QX-314 is then permanently present in the channel.
D000818:Animals; D001369:Axons / Q000378:metabolism*; D049832:Decapodiformes; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008012:Lidocaine / Q000031:analogs & derivatives / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism* / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology*
D007473:Ion Channels; C012647:QX-314; D013779:Tetrodotoxin; D008012:Lidocaine; D012964:Sodium