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Tonic GABAA receptor-mediated currents in human brain

Authors

  • Annalisa Scimemi,

    1. Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
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  • Anna Andersson,

    1. Epilepsy Research Group, Section of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Göteborg University, Sweden
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  • Joost H. Heeroma,

    1. Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
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  • Joakim Strandberg,

    1. Epilepsy Research Group, Section of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Göteborg University, Sweden
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  • Bertil Rydenhag,

    1. Epilepsy Research Group, Section of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Göteborg University, Sweden
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  • Andrew W. McEvoy,

    1. Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
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  • Maria Thom,

    1. Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
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  • Fredrik Asztely,

    1. Epilepsy Research Group, Section of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Göteborg University, Sweden
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  • Matthew C. Walker

    1. Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
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Dr M. C. Walker
E-mail: m.walker@ion.ucl.ac.uk

Abstract

GABAA receptors can mediate both phasic (synaptic) and tonic (extrasynaptic) forms of inhibition. It has been proposed that tonic inhibition plays a critical part in controlling neuronal and network excitability. Although tonic GABAA receptor-mediated currents have been well characterized in rodents, their existence in human tissue has yet to be demonstrated. Here we show that tonic currents can be recorded from human tissue obtained from patients undergoing temporal lobectomies. Tonic GABAA receptor-mediated currents were present in pyramidal cells and interneurons in layer V-VI of temporal neocortex and granule cells in the dentate gyrus. These tonic currents have cell type-specific pharmacologies, opening up the possibility of targeted therapeutics.

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