Possible Interaction: Gamma-Aminobutyric Acid and Sevoflurane

“Background:Propofol and sevoflurane display additivity for γ-aminobutyric acid receptor activation , loss of consciousness, and tolerance of skin incision.”

“Results:Both propofol and sevoflurane alone enhanced the amplitude of GABAA receptor responses to submaximal concentrations of GABA in a dose-dependent manner.”

“At GABA (1 mM), peak currents and 10-90%-rise times decreased with increasing sevoflurane concentrations.”

“However, sevoflurane additively potentiated the tonic GABA currents in both cells.”

“In conclusion, the present study suggests that sevoflurane and halothane increase the accumulation of GABA by inducing the reverse transport of this neurotransmitter.”

“The accumulation of [3H]GABA was significantly increased by sevoflurane (0.058, 0.11, 0.23, 0.46, and 0.93 mM) and halothane (0.006, 0.012, 0.024, 0.048, 0072, and 0.096 mM) with an EC50 of 0.26 mM and 35 μM, respectively.”

“Treatment with the Ca2+ channel blocker Cd2+ restored the frequency of mIPSCs to the control level, indicating sevoflurane ’s strong presynaptic suppression of γ‐aminobutyric acid release in the striatum.”

“Patch-clamp recordings revealed that sevoflurane (0.23 mM) slightly enhanced the amplitude of tonic GABA current in the frontal cortical neurons; however, these effects were not strong enough to alter discharge properties of cortical neurons.”

“Conclusions:The current study provides evidence that amnestic concentrations of sevoflurane inhibit LTP of hippocampal CA1 neurons through γ-aminobutyric acid –mediated mechanisms, and these actions seem to account for the effects of amnestic sevoflurane on synaptic plasticity.”

“Rapid application of sevoflurane-induced ICl by itself, with …(-3) M. Although a pretreatment with 10(-3) M sevoflurane … GABA (3 x 10(-6) M)-induced ICl and suppressed the peak amplitude when the GABA … by any concentration of GABA (from 3 x 10(-6) to 10(-4) M).”

“4 At low concentrations (between 3 × 10−4 and 10−3 m), Sev markedly enhanced the 10−6 m GABA induced current (IGABA) but reduced the IGABA with accelerating desensitization accompanied by a ‘hump’ current after washout at high concentrations (higher than 2 × 10−3 m).”

“5 Sev , 10−3 m potentiated the current induced by low concentrations of GABA (between 10−7 and 3 × 10−6 m) but reduced the current induced by high concentrations (higher than 10−5 m) of GABA with a clear acceleration of IGABA desensitization.”