Block of acetylcholine-activated ion channels by an uncharged local anaesthetic

Abstract

Amine local anesthetic compounds (procaine, lignocaine and related molecules) presumably depress electrical activity in nerve and muscle cells by binding to sites within ion channels and blocking current flow. Such mechanisms may account for the effects of the local anesthetics on both the voltage-dependent Na current and the post-synaptic ACh-activated ionic current. Recently, strong evidence for block of ion channels by cationic drug molecules was obtained by recording current from single ACh-activated channels in the presence of permanently charged quaternary derivatives of lignocaine. Most amine local anesthetic compounds are weak bases, present in both charged and uncharged forms at physiological pH. Whether a charged group is essential for blockade of ion channels is unknown. The action of the uncharged local anesthetic benzocaine (ethyl-4-aminobenzoate) on postsynaptic ACh-activated end-plate current and extrajunctional single channel current of frog muscle was studied. Benzocaine evidently blocks ACh-activated ion channels.