title: General anesthetics have differential inhibitory effects on gap junction channels and hemichannels in astrocytes and neurons.
abstract: Astrocytes represent a major non-neuronal cell population actively involved in brain functions and pathologies. They express a large amount of gap junction proteins that allow communication between adjacent glial cells and the formation of glial networks. In addition, these membrane proteins can also operate as hemichannels, through which "gliotransmitters" are released, and thus contribute to neuroglial interaction. There are now reports demonstrating that alterations of astroglial gap junction communication and/or hemichannel activity impact neuronal and synaptic activity. Two decades ago we reported that several general anesthetics inhibited gap junctions in primary cultures of astrocytes (Mantz et al., (1993) Anesthesiology 78(5):892-901). As there are increasing studies investigating neuroglial interactions in anesthetized mice, we here updated this previous study by employing acute cortical slices and by characterizing the effects of general anesthetics on both astroglial gap junctions and hemichannels. As hemichannel activity is not detected in cortical astrocytes under basal conditions, we treated acute slices with the endotoxin LPS or proinflammatory cytokines to induce hemichannel activity in astrocytes, which in turn activated neuronal hemichannels. We studied two extensively used anesthetics, propofol and ketamine, and the more recently developed dexmedetomidine. We report that these drugs have differential inhibitory effects on gap junctional communication and hemichannel activity in astrocytes when used in their respective, clinically relevant concentrations, and that dexmedetomidine appears to be the least effective on both channel functions. In addition, the three anesthetics have similar effects on neuronal hemichannels. Altogether, our observations may contribute to optimizing the selection of anesthetics for in vivo animal studies.
authors.affiliation: Collège De France, Center for Interdisciplinary Research in Biology (CIRB)/Centre National De La Recherche Scientifique, Unité Mixte De Recherche 7241/Institut National De La Santé Et De La Recherche Médicale U1050, Paris Cedex 05, France.|University Pierre Et Marie Curie, Paris, France.|MEMOLIFE Laboratory of Excellence and Paris Science Lettre Research University, Paris, France.
authors.forename: Xinhe
authors.initials: X
authors.lastname: Liu
authors.affiliation: Collège De France, Center for Interdisciplinary Research in Biology (CIRB)/Centre National De La Recherche Scientifique, Unité Mixte De Recherche 7241/Institut National De La Santé Et De La Recherche Médicale U1050, Paris Cedex 05, France.|University Pierre Et Marie Curie, Paris, France.|MEMOLIFE Laboratory of Excellence and Paris Science Lettre Research University, Paris, France.
authors.forename: Ester
authors.initials: E
authors.lastname: Gangoso
authors.affiliation: Collège De France, Center for Interdisciplinary Research in Biology (CIRB)/Centre National De La Recherche Scientifique, Unité Mixte De Recherche 7241/Institut National De La Santé Et De La Recherche Médicale U1050, Paris Cedex 05, France.|University Pierre Et Marie Curie, Paris, France.|MEMOLIFE Laboratory of Excellence and Paris Science Lettre Research University, Paris, France.
authors.forename: Chenju
authors.initials: C
authors.lastname: Yi
authors.affiliation: Collège De France, Center for Interdisciplinary Research in Biology (CIRB)/Centre National De La Recherche Scientifique, Unité Mixte De Recherche 7241/Institut National De La Santé Et De La Recherche Médicale U1050, Paris Cedex 05, France.|University Pierre Et Marie Curie, Paris, France.|MEMOLIFE Laboratory of Excellence and Paris Science Lettre Research University, Paris, France.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Jeanson
authors.affiliation: Département D'anesthésie Et De Réanimation, HUPNVS, Université Paris Diderot, Paris, France.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Kandelman
authors.affiliation: Service D'anesthésie Réanimation, Hôpital Européen Georges Pompidou, Paris Descartes University, Paris, France.|Unité D'histopathologie Humaine Et Modèles Animaux Département Infection Et Epidémiologie Institut Pasteur 25, Rue Du Docteur Roux, Paris, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Mantz
authors.affiliation: Collège De France, Center for Interdisciplinary Research in Biology (CIRB)/Centre National De La Recherche Scientifique, Unité Mixte De Recherche 7241/Institut National De La Santé Et De La Recherche Médicale U1050, Paris Cedex 05, France.|University Pierre Et Marie Curie, Paris, France.|MEMOLIFE Laboratory of Excellence and Paris Science Lettre Research University, Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Giaume
mesh_terms: D018681:Anesthetics, General / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D017630:Connexins / Q000378:metabolism*; D020927:Dexmedetomidine / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007649:Ketamine / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology; D046509:Tissue Culture Techniques; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D018681:Anesthetics, General; D017630:Connexins; D008070:Lipopolysaccharides; D049452:Green Fluorescent Proteins; D020927:Dexmedetomidine; D007649:Ketamine; D015742:Propofol
keywords: cerebral cortex; connexin channels; dexmedetomidine; glial cells; ketamine; propofol