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Xenon acts by inhibition of glutamatergic neurotransmission in Caenorhabditis elegans: A-471

Nagele, P.; Metz, L. B.; Crowder, C. M.

European Journal of Anaesthesiology: May 2005 - Volume 22 - Issue - p 123
Pharmacology

Department of Anesthesiology, Medical University of Vienna, Vienna, Austria

Background and Goal of Study: The mechanism of action of the anesthetic gas xenon is ill-defined. In vitro electrophysiological studies implicate antagonism of several types of postsynaptic ion channels, the most prominent of which is the NMDA subtype glutamate receptor1, as potential mechanisms of action. We have previously provided genetic evidence that nitrous oxide (N2O), an anesthetic gas similar to xenon, acts through inhibition of the NM DA receptor in vivo2. The goal of this study was to determine the behavioral effects of xenon in the nematode C. elegans and furthermore to test the hypothesis that the main mechanism of action of xenon is through inhibition of NMDA subtype glutamatergic neurotransmission.

Materials and Methods: Well-fed one-day post-L4 adult C. elegans animals were transferred by platinum wire to agar pads with no bacteria; the pads were placed into glass chambers containing either a 75%:25% xenon:O2 mixture or air. After a 10-min incubation period, locomotion was scored over a seven-minute period. At least 10 animals were scored for each data point or strain.

Results and Discussions: Xenon produced behavioral effects similar to those seen with N2O. Like N2O but unlike volatile anesthetics, xenon did not affect gross locomotion but markedly changed the character of movement. Xenon greatly reduced the frequency of reversals of direction of movement in wild-type worms, an unusual behavioral effect otherwise only seen in worms with reduced glutamatergic neurotransmission. The EC50 for xenon was 19% ± 0.9%. Surprisingly, a mutant lacking the NMDA receptor NMR-1 was normally sensitive to xenon whereas being resistant to N2O. However, a non-NMDA receptor null mutant glr-1(ky176), which is sensitive to N2O, was not affected by and thus resistant to xenon.

Conclusion(s): Our findings show that the main mechanism of action of xenon in C. elegans is by inhibiting glutamatergic neurotransmission. The sensitivity of the NMDA receptor null mutant to xenon argues that, unlike N2O, xenon does not act through the NMDA receptor; rather a non-NMDA receptor is more central to xenon's action in C. elegans.

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References:

1 Nature 396:324 (1998)
2 Proc Natl Acad Sci 101:8791-6 (2004)
© 2005 European Society of Anaesthesiology