Ketamine decreases the open time of single-channel currents activated by acetylcholine

Abstract

Patch clamp techniques have been used to study the effects of ketamine on single-channel currents activated by acetylcholine from cell-attached patches of BC3H1 mouse tumor cells grown in culture. Ketamine decreased the average lifetime of the channels, although its effects were not consistent with a sequential blocking model in which molecules of drug bind to the open channel to occlude it. The reduction in channel lifetime produced by ketamine was dose-dependent and occurred at clinically relevant concentrations. At 3 μM, which is the plasma level attained after an intravenous dose of 2 mg/kg, average channel lifetime should be reduced by about 17%. This finding may help to explain clinical reports that ketamine can potentiate neuromuscular block produced by vecuronium or d-tubocurarine. In addition, similar effects on transmitter-activated channels in the central nervous system may underlie some of the clinical properties of ketamine.