Local anaesthetics transiently block currents through single acetylcholine‐receptor channels.

Abstract

Single channel currents through acetylcholine receptor channels (ACh channels) were recorded at chronically denervated frog muscle extrajunctional membranes in the absence and presence of the lidocaine derivatives QX-222 [2-(trimethylamino)-N-2,6-dimethylacetamide] and QX-314 [2-(triethylamino)-N-2,6-dimethylacetamide)]. The current wave forms due to the opening and closing of single ACh channels (activated by suberyldicholine) normally are square pulses. These single pulses appear to be chopped into bursts of much shorter pulses, when the drug QX-222 is present in addition to the agonist. The mean duration of the bursts is comparable to or longer than the normal channel open time, and increases with increasing drug concentration. The duration of the short pulses within a burst decreases with increasing drug concentration. Drug molecules reversibly block open end-plate channels and that the flickering within a burst represents this fast, repeatedly occuring reaction. The voltage dependence of the reaction rates involved, suggested that the site of blocking reaction is in the center of the membrane, probably inside the ionic channel.