title: Astrocytic GABA transporter activity modulates excitatory neurotransmission.
abstract: Astrocytes are ideally placed to detect and respond to network activity. They express ionotropic and metabotropic receptors, and can release gliotransmitters. Astrocytes also express transporters that regulate the extracellular concentration of neurotransmitters. Here we report a previously unrecognized role for the astrocytic GABA transporter, GAT-3. GAT-3 activity results in a rise in astrocytic Na+concentrations and a consequent increase in astrocytic Ca2+through Na+/Ca2+exchange. This leads to the release of ATP/adenosine by astrocytes, which then diffusely inhibits neuronal glutamate release via activation of presynaptic adenosine receptors. Through this mechanism, increases in astrocytic GAT-3 activity due to GABA released from interneurons contribute to 'diffuse' heterosynaptic depression. This provides a mechanism for homeostatic regulation of excitatory transmission in the hippocampus.
authors.affiliation: Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.|Faculty of Health and Medical Sciences, Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Boddum
authors.affiliation: Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Jensen
authors.affiliation: Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: Vincent
authors.initials: V
authors.lastname: Magloire
authors.affiliation: Faculty of Health and Medical Sciences, Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
authors.forename: Uffe
authors.identifier: 0000-0001-9050-7806
authors.initials: U
authors.lastname: Kristiansen
authors.affiliation: Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: Dmitri A
authors.identifier: 0000-0001-9539-9947
authors.initials: DA
authors.lastname: Rusakov
authors.affiliation: Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: Ivan
authors.identifier: 0000-0003-1266-6988
authors.initials: I
authors.lastname: Pavlov
authors.affiliation: Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Walker
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D050485:GABA Plasma Membrane Transport Proteins / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D007395:Interneurons / Q000378:metabolism; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D050485:GABA Plasma Membrane Transport Proteins; C493417:Slc6a11 protein, rat; D019831:Sodium-Calcium Exchanger; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000255:Adenosine Triphosphate; D012964:Sodium; D000241:Adenosine; D002118:Calcium