The Effects of Volatile Anesthetics on the Extrace

Authors: Paulo H C Diniz Cristina Guatimosim Nancy S Binda Flávia L P Costa Marcus V Gomez Renato S Gomez

Publish Date: 2013/10/01

Volume: 34, Issue: 1, Pages: 71-81

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Abstract

GABA is an inhibitory neurotransmitter that appears to be associated with the action of volatile anesthetics These anesthetics potentiate GABAinduced postsynaptic currents by synaptic GABAA receptors although recent evidence suggests that these agents also significantly affect extrasynaptic GABA receptors However the effect of volatile anesthetics on the extracellular concentration of GABA in the central nervous system has not been fully established In the present study rat brain cortical slices loaded with 3HGABA were used to investigate the effect of halothane and sevoflurane on the extracellular accumulation of this neurotransmitter The accumulation of 3HGABA was significantly increased by sevoflurane 0058 011 023 046 and 093 mM and halothane 0006 0012 0024 0048 0072 and 0096 mM with an EC50 of 026 mM and 35 μM respectively TTX blocker of voltagedependent Na+ channels EGTA an extracellular Ca2+ chelator and BAPTAAM an intracellular Ca2+ chelator did not interfere with the accumulation of 3HGABA induced by 023 mM sevoflurane and 0048 mM halothane SKF 89976A a GABA transporter type 1 GAT1 inhibitor reduced the sevoflurane and halothaneinduced increase in the accumulation of GABA by 57 and 63  respectively Incubation of brain cortical slices at low temperature 17 °C a condition that inhibits GAT function and reduces GABA release through reverse transport reduced the sevoflurane and halothaneinduced increase in the accumulation of 3HGABA by 82 and 75  respectively relative to that at normal temperature 37 °C Ouabain a Na+/K+ ATPase pump inhibitor which is known to induce GABA release through reverse transport abolished the sevoflurane and halothane effects on the accumulation of 3HGABA The effect of sevoflurane and halothane did not involve glial transporters because βalanine a blocker of GAT2 and GAT3 did not inhibit the effect of the anesthetics In conclusion the present study suggests that sevoflurane and halothane increase the accumulation of GABA by inducing the reverse transport of this neurotransmitter Therefore volatile anesthetics could interfere with neuronal excitability by increasing the action of GABA on synaptic and extrasynaptic GABA receptors

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