title: Contrasting synaptic actions of the inhalational general anesthetics isoflurane and xenon.
abstract: BACKGROUND
  The mechanisms by which the inhalational general anesthetics isoflurane and xenon exert their effects are unknown. Moreover, there have been surprisingly few quantitative studies of the effects of these agents on central synapses, with virtually no information available regarding the actions of xenon.
  
  
  METHODS
  The actions of isoflurane and xenon on gamma-aminobutyric acid-mediated (GABAergic) and glutamatergic synapses were investigated using voltage-clamp techniques on autaptic cultures of rat hippocampal neurons, a preparation that avoids the confounding effects of complex neuronal networks.
  
  
  RESULTS
  Isoflurane exerts its greatest effects on GABAergic synapses, causing a marked increase in total charge transfer (by approximately 70% at minimum alveolar concentration) through the inhibitory postsynaptic current. This effect is entirely mediated by an increase in the slow component of the inhibitory postsynaptic current. At glutamatergic synapses, isoflurane has smaller effects, but it nonetheless significantly reduces the total charge transfer (by approximately 30% at minimum alveolar concentration) through the excitatory postsynaptic current, with the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor-mediated components being roughly equally sensitive. Xenon has no measurable effect on GABAergic inhibitory postsynaptic currents or on currents evoked by exogenous application of GABA, but it substantially inhibits total charge transfer (by approximately 60% at minimum alveolar concentration) through the excitatory postsynaptic current. Xenon selectively inhibits the NMDA receptor-mediated component of the current but has little effect on the AMPA/kainate receptor-mediated component.
  
  
  CONCLUSIONS
  For both isoflurane and xenon, the most important targets appear to be postsynaptic. The authors' results show that isoflurane and xenon have very different effects on GABAergic and glutamatergic synaptic transmission, and this may account for their differing pharmacologic profiles.
authors.affiliation: The Blackett Laboratory, Imperial College of Science, Technology, and Medicine, London, United Kingdom.
authors.forename: S L
authors.initials: SL
authors.lastname: de Sousa
authors.forename: R
authors.initials: R
authors.lastname: Dickinson
authors.forename: W R
authors.initials: WR
authors.lastname: Lieb
authors.forename: N P
authors.initials: NP
authors.lastname: Franks
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004594:Electrophysiology; D018698:Glutamic Acid / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D014978:Xenon / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D018685:Anesthetics, Inhalation; D014978:Xenon; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D007530:Isoflurane