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Both N2O and xenon potentiate GABA gating at recombinant GABAA receptors

Hapfelmeier, G.; Haseneder, R.; Schneck, H.; Kochs, E.

Section Editor(s): Graf, B. M.; Weimann, J.

European Journal of Anaesthesiology: 2000 - Volume 17 - Issue - p 7
Abstracts: Third Meeting of the International Society for Medical Gases (ISMG); Heidelberg, Germany, 29 September-1 October 1999
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Klinikum r.d. Isar, Technische Universität München, Germany

ABSTRACT NO: 013

Introduction: Although both N2O and xenon (Xe) are anaesthetics used in clinical practice, not much is known about their effects on the GABAA receptor (GABAAR). N2O was shown to increase the GABA response [1]. We studied both gases on a recombinant GABAAR.

Methods: Two types of GABAAR from rat brain (α1β2γ2 or α1β2) were expressed in HEK 293 cells. Currents elicited by GABA were recorded using standard patch-clamp techniques (whole cell mode) and a system for ultrafast exchange of solutions (<0.1 ms). GABA 1 mM or 0.01 mM were applied to the patches alone or dissolved in saturated solutions of the respective gases (room temperature, atmospheric pressure).

Results: In both types of GABAAR, the addition of N2O or Xe increased the current elicited by 0.01 mM GABA (corresponding to EC31 ± 15) by a mean of 69% (N2O, α1β2γ2) or 39% (Xe, α1β2γ2), and by 88% (N2O, α1β2) or 40% (Xe, α1β2) respectively. The 10-90% rise times decreased by 31% (N2O, α1β2γ2) or 30% (Xe, α1β2γ2), and by 30% (N2O, α1β2) or 37% (Xe, α1β2) respectively. Saturated GABA response as evoked by 1 mM GABA was not affected. Helium was used as control and remained without effect on peak currents or rise times.

Conclusions: The effects of the small gases N2O and Xe on a recombinant mammalian GABAAR are very similar in the two subunit combinations studied. The potentiation of the peak current and the shortening of the rise time suggest an increase in the agonist affinity to the GABAAR under the influence of N2O or Xe.

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References:

1 Dzoljic M, van Duijn B. Anesthesiology 1998; 88: 473-480.

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The publication of this supplement has been supported by the sponsors of the Third ISMG Meeting: Abbott, AGA, AstraZeneca, Dräger, Janssen, Medex Medical, Messer Austria, Ohmeda, Pharmacia & Upjohn, Scott Medical Products, Siemens

© 2000 European Society of Anaesthesiology