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GENERAL ARTICLES

Nitrous Oxide and Xenon Increase the Efficacy of GABA at Recombinant Mammalian GABA_A Receptors

Gerhard Hapfelmeier, MD^*, Walter Zieglgänsberger, MD, PhD, Rainer Haseneder^*, Hajo Schneck, MD, and Eberhard Kochs, MD^*

*Department of Anesthesiology, Klinikum rechts der Isar, Technische Universität München, München; Max-Planck-Institute of Psychiatry, Munich; and Kreisklinik Ebersberg, Ebersberg, Germany

Address correspondence and reprint requests to Gerhard Hapfelmeier, MD, Klinik für Anaesthesiologie der Technischen Universität München, Klinikum rechts der Isar, Ismaninger Straße 22, D-81675 München, Germany. Address e-mail to hapfelmeier @mpipsykl.mpg.de.

We investigated the interactions between recombinant gamma-aminobutyric acid receptor complex (GABA_AR) and nitrous oxide (N₂O) or xenon (Xe). Human embryonic kidney cells (HEK 293) were transfected with rat cDNA for ₁ß_22L or for ₁ß₂ recombinant GABA_AR subunits. Patch clamp techniques were used in the whole-cell mode to evaluate the effect of N₂O and Xe on GABA-induced currents. A piezo-driven "liquid filament switch" was used for fast application. Both N₂O (100%, 29.2 mM) and Xe (100%, 3.9 mM) reversibly increased GABA-induced currents through the ₁ß_22L and the ₁ß₂ GABA_AR channels. The potentiating effect of N₂O or Xe on peak currents was prominent at small GABA concentrations (10^-7 to 10^-5 M). The addition of N₂O or Xe increased the efficacy of GABA (10^-7 to 10^-3 M). Both N₂O and Xe significantly decreased the risetime_(10%–90%) of the currents elicited by small GABA concentrations. At the concentrations used, neither N₂O nor Xe had an intrinsic effect. We conclude that, similar to other anesthetics, both N₂O and Xe increase the efficacy of GABA at the GABA_AR and enhance inhibitory GABAergic synaptic transmission. {abs}

Implications: The anesthetic gases nitrous oxide (laughing gas) and xenon increase the activity of a mammalian GABA_A receptor. This receptor is held responsible for the inhibition of important actions of the human brain, e.g., maintenance of consciousness and awareness.

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