title: Effects of halothane on GABAergic and glutamatergic transmission in isolated hippocampal nerve-synapse preparations.
abstract: We evaluated the effects of halothane on synaptic and extrasynaptic GABA(A) 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 GABA(A) 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 GABA(A)-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 GABA(A) 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 action-effecting 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.
authors: Research Division of Neurophysiology, Kitamoto Hospital, 3-7-6 Kawarasone, Koshigaya 343-0821, Japan. n-kotani@agate.plala.or.jp
authors: N
authors: N
authors: Kotani
authors: M
authors: M
authors: Wakita
authors: M C
authors: MC
authors: Shin
authors: S
authors: S
authors: Ogawa
authors: K
authors: K
authors: Nonaka
authors: N
authors: N
authors: Akaike
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006221:Halothane / Q000494:pharmacology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D005973:Glutamine; D005680:gamma-Aminobutyric Acid; D006221:Halothane