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ANESTHETIC PHARMACOLOGY

The Differential Effects of the Nonimmobilizer 1,2-Dichlorohexafluorocyclobutane (F6, 2N) and Isoflurane on Extrasynaptic Gamma-Aminobutyric Acid_A Receptors

Department of Anesthesiology, University of Wisconsin, Madison

Address correspondence and reprint requests to M. Perouansky, room 43, Bardeen labs, 1300 University Ave., Madison, WI 53792-3272. Address e-mail to mperouansky{at}wiscmail.wisc.edu.

The nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6; also known as 2N) causes amnesia and seizures at concentrations less than and more than, respectively, than that predicted to cause immobility (MAC_pred). The molecular and cellular basis of these effects is not known. We reported previously that F6 has no effect on synaptic gamma aminobutyric acid (GABA)_A receptors located on the somata of hippocampal pyramidal cells. However, in hippocampal neurons, GABA_A receptors that are located subsynaptically have different pharmacologic properties from those at extrasynaptic sites, and these classes of receptors may serve different physiologic functions. Therefore, we investigated the effects of F6 and isoflurane on currents mediated predominantly by extrasynaptic GABA_A receptors harvested from hippocampal neurons by exposing nucleated excised patches to brief, high-concentration pulses of GABA. We found that extrasynaptic GABA_A receptors in the majority of neurons located in the pyramidal cell layer are insensitive to F6 at concentrations up to 110 µM, although receptors harvested from one putative interneuron were potently inhibited by 43 µM of F6. By contrast, isoflurane consistently reduced the peak amplitude and slowed deactivation of currents mediated by extrasynaptic receptors, similar to its effect on synaptic receptors. These results demonstrate the selective sensitivity of extrasynaptic GABA_A receptors on pyramidal neurons to isoflurane but not F6.

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				E. D. Zarnowska, R. A. Pearce, A. A. Saad, and M. Perouansky The {gamma}-Subunit Governs the Susceptibility of Recombinant {gamma}-Aminobutyric Acid Type A Receptors to Block by the Nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6, 2N) Anesth. Analg., August 1, 2005; 101(2): 401 - 406. [Abstract] [Full Text] [PDF]

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