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ANESTHETIC PHARMACOLOGY

General Anesthetics Inhibit Gap Junction Communication in Cultured Organotypic Hippocampal Slices

Division of Cellular and Molecular Biology, Toronto Western Research Institute, Departments of Anesthesia & Pain Management, Physiology and Medicine (Neurology), University of Toronto, University Health Network, Toronto, Ontario, Canada

Address correspondence and reprint requests to Hossam El Beheiry, MBBCh, PhD, FRCPC, Department of Anesthesia & Pain Management, Toronto Western Hospital, University Health Network, 399 Bathurst Street, 2MC405, Toronto, ON, Canada M5T 2S8. Address e-mail to beheiry{at}uhnres.utoronto.ca.

Gap junctions are protein channels that directly connect the cytosol of neighboring cells, thus forming electrical synapses and promoting synchronous neuronal activities. Such activities lead to the initiation and propagation of electroencephalogram oscillations implicated in cognition and consciousness. In this study, we investigated the effects of propofol, thiopental, and halothane on gap junction communication in cultured organotypic hippocampal slices by recovery of fluorescence after photo bleaching (FRAP) technique and electrophysiological recordings. Propofol 15 µM and thiopental 10 µM attenuated gap junction communication in slice cultures by 46.7% ± 4.5% and 48.8% ± 5.5%, respectively, as measured by FRAP. Smaller concentrations of propofol 5 µM and thiopental 2 µM did not change gap junction coupling. Accompanying the decreased gap junction communication, hippocampus slice cultures exposed to propofol 15 µM and thiopental 10 µM were found to have reduced electrophysiologic spontaneous discharges and primary after discharges evoked by a tetanic train of 50 Hz for 2 s. On the other hand, halothane 0.64 mM, a concentration slightly larger than twice its minimum alveolar concentration had no effect on gap junction coupling while halothane 2.8 mM blocked FRAP by 70%. The current study illustrates that anesthetic concentrations of propofol and thiopental, but not halothane, attenuate gap junction communication in cultured hippocampal slices. Suppression of gap junction function could compound the mechanisms of anesthetic actions.

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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