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Anesth Analg 2004;99:409-415
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000131969.46439.71


ANESTHETIC PHARMACOLOGY

Halothane and Propofol Modulation of {gamma}-Aminobutyric AcidA Receptor Single-Channel Currents

Akira Kitamura, MD PhD*,{dagger}, Ryoichi Sato, MD PhD*, William Marszalec, PhD*, Jay Z. Yeh, PhD*, Ryo Ogawa, MD PhD{dagger}, and Toshio Narahashi, DVM PhD*

*Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois; and {dagger}Department of Anesthesiology, Nippon Medical School, Tokyo, Japan

Address correspondence and reprint requests to Toshio Narahashi, DVM, PhD, Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, IL 60611. Address e-mail to narahashi{at}northwestern.edu

Halothane and propofol enhance the activity of the {gamma}-aminobutyric acid (GABA) system, which is one of the most important systems in the mechanism of anesthesia. To determine whether halothane and propofol enhance GABAergic responses by the same mechanism, we performed single-channel patch-clamp experiments with rat cortical neurons in primary culture. Each of the open-time and closed-time distributions of GABAA receptor single channels was expressed by a sum of fast and slow time constants. Neither halothane nor propofol changed the single-channel conductance. Halothane increased the probability of the channel being open via a prolongation of the slow phase of open time, whereas propofol increased the channel open probability via a shortening of the slow phase of closed time. Thus, although both halothane and propofol augmented the channel open probability, thereby causing an increase in charge transfer during inhibitory transmitter action, they acted by different mechanisms.

IMPLICATIONS: Although both halothane and propofol increase {gamma}-aminobutyric acid (GABA)-mediated synaptic inhibition, thereby causing anesthesia, the underlying mechanisms at the single GABA receptor channels have been shown to be different by using the patch-clamp technique.




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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 © 2004 by the International Anesthesia Research Society.