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Anesth Analg 2000;91:1542-1549
© 2000 International Anesthesia Research Society


GENERAL ARTICLES

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

Gerhard Hapfelmeier, MD*, Walter Zieglgänsberger, MD, PhD{dagger}, Rainer Haseneder*, Hajo Schneck, MD{ddagger}, and Eberhard Kochs, MD*

*Department of Anesthesiology, Klinikum rechts der Isar, Technische Universität München, München; {dagger}Max-Planck-Institute of Psychiatry, Munich; and {ddagger}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 (GABAAR) and nitrous oxide (N2O) or xenon (Xe). Human embryonic kidney cells (HEK 293) were transfected with rat cDNA for {alpha}1ß2{gamma}2L or for {alpha}1ß2 recombinant GABAAR 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 {alpha}1ß2{gamma}2L and the {alpha}1ß2 GABAAR 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 GABAAR and enhance inhibitory GABAergic synaptic transmission. {abs}

Implications: The anesthetic gases nitrous oxide (laughing gas) and xenon increase the activity of a mammalian GABAA 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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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2000 by the International Anesthesia Research Society.