'Concentration-clamp' study of gamma-aminobutyric-acid-induced chloride current kinetics in frog sensory neurones

Abstract

Kinetics of the activation and desensitization phases of gamma-aminobutyric acid (GABA)-induced Cl- current (ICl) were studied in single frog sensory neurones using the 'concentration-clamp' technique which enables perfusion of drugs with the time constant of about 3 ms. Both activation and desensitization phases of GABA response consisted of a single exponential at low concentrations and a double exponential at high concentrations. The time constant of the fast kinetic component in each phase was relatively stable, about 5 ms for activation and 3 s for desensitization over concentrations from 3 X 10(-5) to 3 X 10(-4) M, whereas those of the slow kinetic component decreased with increasing concentrations. The two kinetic components in both phases showed the same reversal potential. The slow and fast activation components recovered sensitivity from desensitization with different time courses: the recovery rate of the fast activation component was slow and that of the slow one, rapid. The peak ICl elicited at GABA concentrations below 10(-5) M increased disproportionally at more negative membrane potentials, thereby suggesting that the activation kinetics is voltage dependent. The steady-state ICl-voltage relationship obtained with less than 10(-5) M-GABA showed a non-linearity, probably due to voltage dependence of activation rather than that of desensitization kinetics. These results suggest the presence of at least two different GABA receptor-Cl- ionophore complexes with a different affinity and kinetics.