title: General anesthetics inhibit gap junction communication in cultured organotypic hippocampal slices.
abstract: 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 microM and thiopental 10 microM 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 microM and thiopental 2 microM did not change gap junction coupling. Accompanying the decreased gap junction communication, hippocampus slice cultures exposed to propofol 15 microM and thiopental 10 microM 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.
authors.affiliation: Division of Cellular and Molecular Biology, Toronto Western Research Institute, Department of Anesthesia & Pain Management, Physiology, University of Toronto, University Health Network, Toronto, Ontario, Canada.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Wentlandt
authors.forename: Marina
authors.initials: M
authors.lastname: Samoilova
authors.forename: Peter L
authors.initials: PL
authors.lastname: Carlen
authors.forename: Hossam
authors.initials: H
authors.lastname: El Beheiry
mesh_terms: D018681:Anesthetics, General / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D002450:Cell Communication / Q000187:drug effects*; D004594:Electrophysiology; D005071:Evoked Potentials; D036681:Fluorescence Recovery After Photobleaching; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000503:physiopathology; D008297:Male; D015742:Propofol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013874:Thiopental / Q000494:pharmacology; D046509:Tissue Culture Techniques
chemical_list: D018681:Anesthetics, General; D018686:Anesthetics, Intravenous; D013874:Thiopental; D015742:Propofol