Interactions between quaternary lidocaine, the sodium channel gates, and tetrodotoxin

M. D. Cahalan, W. Almers

Research output: Contribution to journalArticle

133 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)39-55
Number of pages17
JournalBiophysical Journal
Volume27
Issue number1
DOIs
StatePublished - Jan 1 1979

ASJC Scopus subject areas

  • Biophysics

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