| First Author | Egawa K | Year | 2013 |
| Journal | J Physiol | Volume | 591 |
| Issue | 16 | Pages | 3901-17 |
| PubMed ID | 23732644 | Mgi Jnum | J:212782 |
| Mgi Id | MGI:5582148 | Doi | 10.1113/jphysiol.2013.257162 |
| Citation | Egawa K, et al. (2013) Cl(-) homeodynamics in gap junction-coupled astrocytic networks on activation of GABAergic synapses. J Physiol 591(Pt 16):3901-17 |
| abstractText | 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. |
