Effects of halothane on GABAergic and glutamatergic transmission in isolated hippocampal nerve-synapse preparations

N. Kotani, M. Wakita, M. C. Shin, S. Ogawa, K. Nonaka, N. Akaike

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

We evaluated the effects of halothane on synaptic and extrasynaptic GABAA and glutamate receptor responses using mechanically dissociated rat hippocampal CA3 neurons in which the well isolated neurons retain functional native nerve endings (the 'synaptic bouton' preparation). The preparation allows the simultaneous comparison of extrasynaptic GABAA and glutamate receptors, activated by bath applied GABA and glutamate, respectively, to the synaptic receptors measured as spontaneous and evoked postsynaptic currents. Paired-pulse synaptic responses evoked by focal electrical stimulation were also measured to evaluate any presynaptic effects. Halothane enhanced the extrasynaptic GABAA-receptor mediated postsynaptic responses in a concentration dependent fashion. At clinically relevant concentrations, halothane significantly increased both the amplitude and frequency of spontaneous postsynaptic inhibitory currents (sIPSCs) mediated by synaptic GABAA receptors. The relative amplitude of evoked IPSCs (eIPSCs) was also increased, concurrent with a decrease in failure rate and a significantly decreased eIPSC paired-pulse ratio. Halothane concentration dependently decreased the extrasynaptic glutamate-receptor induced postsynaptic responses but had no effects on spontaneous or evoked excitatory postsynaptic currents. These results suggest that halothane acts predominantly at presynaptic sites at GABAergic synapses to enhance inhibitory transmission at CA3 synapses, although it also increases extra-synaptic GABA responses. At excitatory synapses on to CA3 neurons, halothane has no presynaptic actioneffecting only extrasynaptic receptors. Our results have clarified the locus of effects of the volatile anesthetic halothane at excitatory and inhibitory synapses, drawing somewhat different conclusions from those deduced from slices and culture systems.

Original languageEnglish (US)
Pages (from-to)9-18
Number of pages10
JournalBrain Research
Volume1473
DOIs
StatePublished - Sep 14 2012

Keywords

  • 'Synaptic bouton' preparation
  • Glutamatergic nerve terminal
  • Halothane
  • Presynaptic GABA receptor
  • Spontaneous and evoked EPSCs

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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