KINETICS OF SEVOFLURANE ACTION ON GABA-INDUCED AND GLYCINE-INDUCED CURRENTS IN ACUTELY DISSOCIATED RAT HIPPOCAMPAL-NEURONS

Effects of a new kind of volatile anaesthetics, sevoflurane, on GABA- and glycine-gated chloride current (I-Cl) were examined in single pyra midal neurons acutely dissociated from the rat hippocampal CA1 region, using the voltage-cramp mode of the nystatin-perforated patch-clamp t echnique. Rapid application of sevoflurane-induced I-Cl by itself, wit h the time to peak reduced as the sevoflurane concentration was increa sed from 10(-3) to 3 x 10(-3) M. Although a pretreatment with 10(-3) M sevoflurane enhanced the peak amplitude of GABA (3 x 10(-6) M)-induce d I-Cl and suppressed the peak amplitude when the GABA concentration w as increased to 10(-4) M, the pretreatment decreased the time to peak of the I-Cl induced by any concentration of GABA (from 3 x 10(-6) to 1 0(-4) M). The treatment also accelerated the decay phase of the GABA-i nduced I-Cl. On the other hand, sevoflurane suppressed the peak I-Cl i nduced by 3 x 10(-5) M glycine in a concentration-dependent manner. In the presence of 3 x 10(-4) M sevoflurane, the peak amplitude of the g lycine-induced I-Cl was decreased without changes in EC50 or Hill coef ficients. Pretreatment with 10(-3) M sevoflurane did not affect the ti me to peak of the I-Cl induced by any concentration of glycine (from 3 x 10(-5) to 10(-3) M). Pretreatment with 3 x 10(-8) M strychnine mark edly prolonged the time to peak of the glycine-induced I-Cl. These res ults suggest that sevoflurane modulated the amplitude of the GABA resp onses, depending on the balance of the accelerated activation and deca y phases, and that sevoflurane suppressed the glycine-induced I-Cl in a non-competitive manner without noticeable effect on the kinetics. Th e reversible and differential modulation of GABA(A) and glycine recept ors might underlie a part of the anaesthetic actions and less adverse clinical effects of sevoflurane. (C) 1998 IBRO. Published by Elsevier Science Ltd.