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Anesth Analg 2003;96:443-448
© 2003 International Anesthesia Research Society

ANESTHETIC PHARMACOLOGY

Nitrous Oxide and Xenon Inhibit the Human ({alpha}7)5 Nicotinic Acetylcholine Receptor Expressed in Xenopus Oocyte

Takahiro Suzuki, MD, Kazuyoshi Ueta, MD, Masahiro Sugimoto, MD, Ichiro Uchida, MD, PhD, and Takashi Mashimo, MD, PhD

Department of Anesthesiology, Osaka University Medical School, Japan

Address correspondence and reprint requests to Ichiro Uchida, MD, PhD, Department of Anesthesiology, Osaka University Medical School, Yamadaoka 2–2, Suita, Osaka 565–0871, Japan. Address e-mail to iuchida{at}anes.med.osaka-u.ac.jp

The neuronal nicotinic acetylcholine (nACh) receptor is one of the ligand-gated ion channels that regulate the synaptic release of neurotransmitters in the central nervous system. Recently, neuronal nACh receptors have received attention as a potential target for general anesthetics because many general anesthetics inhibit their functions at clinical concentrations. Several general anesthetics are known to inhibit the homomeric ({alpha}7)5 nACh receptor, a subtype of neuronal nACh receptors, but the effects of two gaseous anesthetics, nitrous oxide (N2O) and xenon (Xe), remain unknown. Using the two-electrode voltage-clamping technique, we investigated the effects of N2O and Xe at the human ({alpha}7)5 nACh receptor expressed in Xenopus oocytes. At clinically relevant concentrations, N2O and Xe reversibly inhibited the ACh-induced currents of the ({alpha}7)5 nACh receptor in a concen-tration-dependent manner. The inhibitory actions of both anesthetics at the ({alpha}7)5 nACh receptor were noncompetitive and voltage-independent. Our results suggest that inhibition of the ({alpha}7)5 nACh receptor by N2O and Xe may play a role in their anesthetic effects.

IMPLICATIONS:The neuronal nicotinic acetylcholine (nACh) receptors have received attention as a potential target for general anesthetics because many general anesthetics inhibit their functions. However, effects of gaseous anesthetics, nitrous oxide, and xenon on the ({alpha}7)5 receptor, a subtype of the nACh receptor, have not been examined. We report that these anesthetics inhibit the ({alpha}7)5 nACh receptor at clinical concentrations.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 2003 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2003 by the International Anesthesia Research Society.