title: Xenon acts by inhibition of non-N-methyl-D-aspartate receptor-mediated glutamatergic neurotransmission in Caenorhabditis elegans.
abstract: BACKGROUND
  Electrophysiologic experiments in rodents have found that nitrous oxide and xenon inhibit N-methyl-D-aspartate (NMDA)-type glutamate receptors. These findings led to the hypothesis that xenon and nitrous oxide along with ketamine form a class of anesthetics with the identical mechanism, NMDA receptor antagonism. Here, the authors ask in Caenorhabditis elegans whether xenon, like nitrous oxide, acts by a NMDA receptor-mediated mechanism.
  
  
  METHODS
  Xenon:oxygen mixtures were delivered into sealed chambers until the desired concentration was achieved. The effects of xenon on various behaviors were measured on wild-type and mutant C. elegans strains.
  
  
  RESULTS
  With an EC50 of 15-20 vol% depending on behavioral endpoint, xenon altered C. elegans locomotion in a manner indistinguishable from that of mutants in glutamatergic transmission. Xenon reduced the frequency and duration of backward locomotion without altering its speed or other behaviors tested. Mutation of glr-1, encoding a non-NMDA glutamate receptor subunit, abolished the behavioral effects of xenon; however, mutation of nmr-1, which encodes the pore-forming subunit of an NMDA glutamate receptor previously shown to be required for nitrous oxide action, did not significantly alter xenon response. Transformation of the glr-1 mutant with the wild-type glr-1 gene partially restored xenon sensitivity, confirming that glr-1 was necessary for the full action of xenon.
  
  
  CONCLUSIONS
  Xenon acts in C. elegans to alter locomotion through a mechanism requiring the non-NMDA glutamate receptor encoded by glr-1. Unlike for the action of nitrous oxide in C. elegans, the NMDA receptor encoded by nmr-1 is not essential for sensitivity to xenon.
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA. nagelep@morpheus.wustl.edu
authors.forename: Peter
authors.initials: P
authors.lastname: Nagele
authors.forename: Laura B
authors.initials: LB
authors.lastname: Metz
authors.forename: C Michael
authors.initials: CM
authors.lastname: Crowder
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D014978:Xenon / Q000494:pharmacology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D014978:Xenon; D018698:Glutamic Acid