Effects of pentobarbitone on acetylcholine-activated channels in mammalian muscle.

Acetylcholine-activated single channel currents were recorded from the extrajunctional region of chronically denervated skeletal muscle of the rat by the patch clamp technique. In control experiments, the cumulative open-time, closed-time and burst length distributions could be well described by the sum of two exponentials. Pentobarbitone decreased the mean open time and increased the time constant of the fast component of the closed time distribution. These effects increased with drug concentration. The mean burst length was relatively independent of pentobarbitone concentration over the range of concentrations used (10-500 microM). These observations are inconsistent with a simple sequential blocking model and it is suggested that pentobarbitone has an allosteric site of action on receptor-channel complexes that makes the open state less stable.