Influences of external Ca 2+ on the GABA-induced chloride current and the efficacy of diazepam in internally perfused frog sensory neurons

Abstract

The effects of extracellular Ca 2+ on the γ-aminobutyric acid (GABA)-induced Cl - current and the efficacy of diazepam in the facilitation of GABA response were studied in frog isolated sensory neurons, using a ‘concentration clamp’ technique which combines a suction pipette (internal perfusion and voltage clamp) and a rapid drug application system. When nominal Ca 2+-free external solution was changed to the solution containing 2 mM Ca 2+, the response elicited by 1 × 10 −5 M GABA was reduced by about 40% of the control obtained in nominal Ca 2+-free solution. The dose-response curve for GABA was shifted to the right without affecting the maximum response. It can be suggested that the application of external Ca 2+ modulates the affinity of the GABA receptor to its agonist, GABA. Diazepam at the concentration of 3 × 10 −6 M shifted the dose-response curve for GABA to the left without changing the maximum reponse with or without external Ca 2+. However, the augmentatory action of diazepam on the GABA response was reduced in the presence of external Ca 2+. Possible mechanisms for inhibitory action of external Ca 2+ on the GABA-gated response and the reduced efficacy of diazepam are discussed.