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 microM, 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.