title: Xenon reduces glutamate-, AMPA-, and kainate-induced membrane currents in cortical neurones.
abstract: BACKGROUND
  The anaesthetic, analgesic, and neuroprotective effects of xenon (Xe) are believed to be mediated by a block of the NMDA (N-methyl-D-aspartate) receptor channel. Interestingly, the clinical profile of the noble gas differs markedly from that of specific NMDA receptor antagonists. The aim of this study was, therefore, to investigate whether Xe might be less specific, also inhibiting the two other subtypes of glutamate receptor channels, such as the alpha-amino-3-hydroxy-5-methyl-4-isoxazolole propionate (AMPA) and kainate receptors.
  
  
  METHODS
  The study was performed on voltage-clamped cortical neurones from embryonic mice and SH-SY5Y cells expressing GluR6 kainate receptors. Drugs were applied by a multi-barreled fast perfusion system.
  
  
  RESULTS
  Xe, dissolved at approximately 3.45 mM in aqueous solution, diminished the peak and even more the plateau of AMPA and glutamate induced currents. At the control EC(50) value for AMPA (29 microM) these reductions were by about 40 and 56% and at 3 mM glutamate the reductions were by 45 and 66%, respectively. Currents activated at the control EC(50) value for kainate (57 microM) were inhibited by 42%. Likewise, Xe showed an inhibitory effect on kainate-induced membrane currents of SH-SY5Y cells transfected with the GluR6 subunit of the kainate receptor. Xe reduced kainate-induced currents by between 35 and 60%, depending on the kainate concentration.
  
  
  CONCLUSIONS
  Xe blocks not only NMDA receptors, but also AMPA and kainate receptors in cortical neurones as well as GluR6-type receptors expressed in SH-SY5Y cells. Thus, Xe seems to be rather non-specific as a channel blocker and this may contribute to the analgesic and anaesthetic potency of Xe.
authors.affiliation: Clinic for Anesthesiology, Ulm, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Dinse
authors.forename: K J
authors.initials: KJ
authors.lastname: Föhr
authors.forename: M
authors.initials: M
authors.lastname: Georgieff
authors.forename: C
authors.initials: C
authors.lastname: Beyer
authors.forename: A
authors.initials: A
authors.lastname: Bulling
authors.forename: H U
authors.initials: HU
authors.lastname: Weigt
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D018091:Receptors, AMPA / Q000187:drug effects; D017470:Receptors, Glutamate / Q000187:drug effects; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014978:Xenon / Q000494:pharmacology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000097806:GluK2 Kainate Receptor
chemical_list: D018685:Anesthetics, Inhalation; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D007608:Kainic Acid; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D014978:Xenon; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000097806:GluK2 Kainate Receptor