title: Cl⁻ homeodynamics in gap junction-coupled astrocytic networks on activation of GABAergic synapses.
abstract: The electrophysiological properties and functional role of GABAergic signal transmission from neurons to the gap junction-coupled astrocytic network are still unclear. GABA-induced astrocytic Cl⁻ flux has been hypothesized to affect the driving force for GABAergic transmission by modulating [Cl⁻]o. Thus, revealing the properties of GABA-mediated astrocytic responses will deepen our understanding of GABAergic signal transmission. Here, we analysed the Cl⁻ dynamics of neurons and astrocytes in CA1 hippocampal GABAergic tripartite synapses, using Cl⁻ imaging during GABA application, and whole cell recordings from interneuron-astrocyte pairs in the stratum lacunosum-moleculare. Astrocytic [Cl⁻]i was adjusted to physiological conditions (40 mm). Although GABA application evoked bidirectional Cl⁻ flux via GABAA receptors and mouse GABA transporter 4 (mGAT4) in CA1 astrocytes, a train of interneuron firing induced only GABAA receptor-mediated inward currents in an adjacent astrocyte. A GAT1 inhibitor increased the interneuron firing-induced currents and induced bicuculline-insensitive, mGAT4 inhibitor-sensitive currents, suggesting that synaptic spillover of GABA predominantly induced the astrocytic Cl⁻ efflux because GABAA receptors are localized near the synaptic clefts. This GABA-induced Cl⁻ efflux was accompanied by Cl⁻ siphoning via the gap junctions of the astrocytic network because gap junction inhibitors significantly reduced the interneuron firing-induced currents. Thus, Cl⁻ efflux from astrocytes is homeostatically maintained within astrocytic networks. A gap junction inhibitor enhanced the activity-dependent depolarizing shifts of reversal potential of neuronal IPSCs evoked by repetitive stimulation to GABAergic synapses. These results suggest that Cl⁻ conductance within the astrocytic network may contribute to maintaining GABAergic synaptic transmission by regulating [Cl⁻]o.
authors.affiliation: Department of Neurophysiology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Egawa
authors.forename: Junko
authors.initials: J
authors.lastname: Yamada
authors.forename: Tomonori
authors.initials: T
authors.lastname: Furukawa
authors.forename: Yuchio
authors.initials: Y
authors.lastname: Yanagawa
authors.forename: Atsuo
authors.initials: A
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000502:physiology; D002712:Chlorides / Q000502:physiology*; D017629:Gap Junctions / Q000502:physiology*; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011963:Receptors, GABA-A / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D002712:Chlorides; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid