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Anesth Analg 2005;101:401-406
© 2005 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000155264.67729.E4

ANESTHETIC PHARMACOLOGY

The {gamma}-Subunit Governs the Susceptibility of Recombinant {gamma}-Aminobutyric Acid Type A Receptors to Block by the Nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6, 2N)

Ewa D. Zarnowska, PhD, Robert A. Pearce, MD, PhD, Abdallah A. Saad, BS, and Misha Perouansky, MD

Department of Anesthesiology, University of Wisconsin, Madison

Address correspondence and reprint requests to Misha Perouansky, MD, 601 Science Dr., Madison, WI 53719. Address e-mail to mperouansky{at}wisc.edu.

To identify anesthetic effects that produce the different components of the complex anesthetic state, the so-called nonanesthetics/nonimmobilizer classes of compounds have been introduced. Because ionotropic {gamma}-aminobutyric acid type A (GABAA) receptors play an important role in the mediation of the central nervous system (CNS) effects of general anesthetics, and their susceptibility to modulation by various drugs depends on subunit composition, we have compared the effect of the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6) on GABAA receptors expressed in human embryonic kidney 293 cells transfected with {alpha}1ß2 versus {alpha}1ß2{gamma}2s subunits. Using rapid perfusion and whole-cell recording techniques, we found that, like isoflurane, F6 blocked GABA-induced currents through {alpha}1ß2 receptors but, unlike isoflurane, the presence of the {gamma}2s subunit conferred complete resistance to block by F6. Also, in contrast to isoflurane, F6 had no effect on deactivation kinetics of GABA-induced currents in either type of receptor. We conclude that modulation of {alpha}ß{gamma} receptors plays little or no role in the actions of F6, but the block of {alpha}ß receptors may contribute to its effects on the CNS.






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 © 2005 by the International Anesthesia Research Society.