title: Tonic GABA(A) receptor-mediated currents in human brain.
abstract: GABA(A) 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 GABA(A) 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 GABA(A) 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.
authors.affiliation: Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Scimemi
authors.forename: Anna
authors.initials: A
authors.lastname: Andersson
authors.forename: Joost H
authors.initials: JH
authors.lastname: Heeroma
authors.forename: Joakim
authors.initials: J
authors.lastname: Strandberg
authors.forename: Bertil
authors.initials: B
authors.lastname: Rydenhag
authors.forename: Andrew W
authors.initials: AW
authors.lastname: McEvoy
authors.forename: Maria
authors.initials: M
authors.lastname: Thom
authors.forename: Fredrik
authors.initials: F
authors.lastname: Asztely
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Walker
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D003900:Desoxycorticosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology; D006801:Humans; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D008564:Membrane Potentials; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010852:Picrotoxin / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D014151:Anti-Anxiety Agents; D003900:Desoxycorticosterone; D018756:GABA Antagonists; D010852:Picrotoxin; D011724:Pyridazines; D011963:Receptors, GABA-A; C009413:tetrahydrodeoxycorticosterone; C049853:gabazine