title: Kinetics of sevoflurane action on GABA- and glycine-induced currents in acutely dissociated rat hippocampal neurons.
abstract: Effects of a new kind of volatile anaesthetics, sevoflurane, on GABA- and glycine-gated chloride current (ICl) were examined in single pyramidal neurons acutely dissociated from the rat hippocampal CA1 region, using the voltage-clamp mode of the nystatin-perforated patch-clamp technique. Rapid application of sevoflurane-induced ICl by itself, with the time to peak reduced as the sevoflurane concentration was increased 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)-induced ICl and suppressed the peak amplitude when the GABA concentration was increased to 10(-4) M, the pretreatment decreased the time to peak of the ICl induced by any concentration of GABA (from 3 x 10(-6) to 10(-4) M). The treatment also accelerated the decay phase of the GABA-induced ICl. On the other hand, sevoflurane suppressed the peak ICl induced 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 glycine-induced ICl was decreased without changes in EC50 or Hill coefficients. Pretreatment with 10(-3) M sevoflurane did not affect the time to peak of the ICl induced by any concentration of glycine (from 3 x 10(-5) to 10(-3) M). Pretreatment with 3 x 10(-8) M strychnine markedly prolonged the time to peak of the glycine-induced ICl. These results suggest that sevoflurane modulated the amplitude of the GABA responses, depending on the balance of the accelerated activation and decay phases, and that sevoflurane suppressed the glycine-induced ICl in a non-competitive manner without noticeable effect on the kinetics. The reversible and differential modulation of GABA(A) and glycine receptors might underlie a part of the anaesthetic actions and less adverse clinical effects of sevoflurane.
authors.affiliation: Department of Internal Medicine I, School of Medicine, Oita Medical University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kira
authors.forename: N
authors.initials: N
authors.lastname: Harata
authors.forename: T
authors.initials: T
authors.lastname: Sakata
authors.forename: N
authors.initials: N
authors.lastname: Akaike
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002469:Cell Separation; D018118:Chloride Channels / Q000187:drug effects* / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008738:Methyl Ethers / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D018685:Anesthetics, Inhalation; D018118:Chloride Channels; D008738:Methyl Ethers; D000077149:Sevoflurane; D005680:gamma-Aminobutyric Acid; D005998:Glycine; D001640:Bicuculline