Effects of thiopental, halothane and isoflurane on the calcium-dependent and -independent release of GABA from striatal synaptosomes in the rat

Abstract

The effects of the anesthetic agents thiopental, halothane and isoflurane on the release of GABA induced by depolarization and/or reversal of the GABA carrier were investigated in a synaptosomal preparation obtained from the rat striatum. Veratridine (1 μM) and KCl (9 mM) elicited a significant Ca 2+-dependent release of [ 3H]GABA. The KCl-evoked release was not significantly modified in the presence of nipecotic acid (10 −5 M), a selective blocker of the neuronal GABA carrier. The [ 3H]GABA release was significantly decreased by ω-conotoxin (10 −7 M, a blocker of the N voltage-dependent Ca 2+ channels, but was affected by neither nifedipine (10 −4 M) nor ω-Aga-IVA (10 −7 M) which block the L and Ca 2+ channels, respectively. Thiopental application (10 −5 to 10 −3 M) was followed by a dose-related, significant, decrease in both the veratridine and KCl-induced releases, whether nipecotic acid was present or not. In contrast, halothane and isoflurane (1–3%) failed to alter [ 3H]GABA release. Altogether, these results suggest that reduction of the depolarization-evoked GABA release might contribute to thiopental anesthesia, but this seems unlikely for volatile anesthetics.