Volatile anesthetic effects on isolated GABA synapses and extrasynaptic receptors

S. K. Ogawa, E. Tanaka, M. C. Shin, N. Kotani, N. Akaike

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The volatile anesthetics enhance GABAergic inhibitory transmission at synaptic and extrasynaptic sites at central neurons. In the present study, we investigated the effects of three volatile anesthetics (isoflurane, enflurane and sevoflurane) on synaptic and extrasynaptic GABAA receptor responses using mechanically dissociated rat hippocampal CA1 neurons in which functional native nerve endings (boutons) were retained. The extrasynaptic GABAA receptors were activated by exogenous GABA application while synaptic ones were assessed by miniature and evoked inhibitory postsynaptic currents (mIPSCs and eIPSCs, respectively). All volatile anesthetics concentration-dependently enhanced the exogenous GABA-induced postsynaptic responses. The structural isomers, isoflurane and enflurane, increased mIPSC frequency while sevoflurane had no effect. None of these anesthetics altered mIPSC amplitudes at their clinically relevant concentrations. Sevoflurane prolonged event kinetics by increasing decay time of mIPSCs and eIPSCs at clinically relevant concentration. On the other hand, both isoflurane and enflurane only prolonged the kinetics of these events at 1 mM of high concentration. For GABAergic eIPSCs, both isoflurane and enflurane decreased the evoked response amplitude and increased the failure rate (Rf), while sevoflurane decreased the amplitude without affecting Rf. These results suggest that isoflurane and enflurane at the clinically relevant concentrations predominantly act on GABAergic presynaptic nerve endings to decrease action potential dependent GABA release. It was concluded that these anesthetics have heterogeneous effects on mIPSCs and eIPSCs with different modulation of synaptic and extrasynaptic GABAA receptors.

Original languageEnglish (US)
Pages (from-to)701-710
Number of pages10
JournalNeuropharmacology
Volume60
Issue number4
DOIs
StatePublished - Mar 1 2011

Keywords

  • GABAergic nerve ending (bouton)
  • Hippocampal neuron
  • Synaptic and extrasynaptic GABA receptors
  • Volatile anesthetic
  • eIPSC
  • mIPSC

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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