Diazepam and (--)-pentobarbital: fluctuation analysis reveals different mechanisms for potentiation of gamma-aminobutyric acid responses in cultured central neurons.

Diazepam and (--)-pentobarbital each potentiate the increase in chloride ion conductance produced by gamma-aminobutyric acid (GABA) i voltage-clamped mouse spinal neurons grown in culture. Fluctuation analysis was used to compare the properties of elementary ion-channel events underlying the chloride conductance produced by GABA alone and during potentiation by the two drugs. Neither drug altered the conductance of an open ion channel, but both drugs affected the kinetics of channel activity. Diazepam increased the frequency of channel openings and either did not affect or slightly increased the average open-channel lifetime, whereas (--)-pentobarbital decreased the frequency of channel openings and increased average open-channel lifetime. These changes in the kinetics of GABA-activated ion channels can quantitatively account for the potentiation of GABA responses observed with the drugs. Thus, the drugs each increase the response to GABA but do not act on channel kinetics in the same manner.