Augmentation of GABA-induced current in frog sensory neurons by pentobarbital

Abstract

The effect of pentobarbital sodium (PB) on the gamma-aminobutyric acid (GABA)-induced macroscopic and microscopic Cl- currents (ICl and iCl, respectively) was studied in the soma membrane of isolated frog sensory neurons using a rapid concentration-jump and patch-clamp technique. The GABA-induced ICl was composed of a transient peak and a steady plateau. PB shifted the concentration-response curve of the GABA-induced peak ICl to the left without affecting the maximum value. The apparent dissociation constant (KD) decreased from 13 microM at control to 8.0, 4.8, and 2.9 microM by adding 10, 30, and 100 microM PB, respectively. PB also shifted the concentration-response curve for the plateau ICl to the left and augmented the maximum value of the plateau, indicating an increase in the available receptor-channel complex. The Hill coefficient (n = 2) in concentration-response curves of both peak and plateau responses was not changed by adding PB. Both the activation and desensitization phases of GABA-induced ICl consisted of two exponential components. PB significantly increased the time constant of slow desensitization component at all concentrations of GABA used. In the "inside-out" configuration, PB markedly increased the open probability (Po) of a GABA-gated single Cl- channel having a conductance of 14.57 +/- 2.3 pS (n = 123) without affecting the single-channel conductance. The increase of Po was due to the prolongation of mean open time (tau of the tau os) and shortening of mean closed time (tau cf and tau cs), resulting in the increase of channel-opening events.(ABSTRACT TRUNCATED AT 250 WORDS)