| First Author | Gómez-Gonzalo M | Year | 2018 |
| Journal | Glia | Volume | 66 |
| Issue | 10 | Pages | 2188-2199 |
| PubMed ID | 30144319 | Mgi Jnum | J:266992 |
| Mgi Id | MGI:6257406 | Doi | 10.1002/glia.23473 |
| Citation | Gomez-Gonzalo M, et al. (2018) Insights into the release mechanism of astrocytic glutamate evoking in neurons NMDA receptor-mediated slow depolarizing inward currents. Glia 66(10):2188-2199 |
| abstractText | The gliotransmitter glutamate in different brain regions modulates neuronal excitability and synaptic transmission through a variety of mechanisms. Among the hallmarks of astrocytic glutamate release are the slow depolarizing inward currents (SICs) in neurons mediated by N-methyl-d-aspartate receptor activation. Different stimuli that evoke Ca(2+) elevations in astrocytes induce neuronal SICs suggesting a Ca(2+) -dependent exocytotic glutamate release mechanism of SIC generation. To gain new insights into this mechanism, we investigated the relationship between astrocytic Ca(2+) elevations and neuronal SICs in mouse hippocampal slice preparations. Here we provide evidence that SICs, occurring either spontaneously or following a hypotonic challenge, are unchanged in the virtual absence of Ca(2+) signal changes at astrocytic soma and processes, including spatially restricted Ca(2+) microdomains. SICs are also unchanged in the presence of Bafilomycin A1 that after prolonged slice incubation depletes glutamate from astrocytic vesicles. We also found that hemichannels and TREK family channels-that recent studies proposed to mediate astrocytic glutamate release - are not involved in SIC generation. SICs are reduced by the volume-sensitive anion channel antagonists diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), quinine and fluoxetine, suggesting a possible contribution of these channels in SIC generation. Direct measurements of astrocytic glutamate release further confirm that hypotonicity-evoked gliotransmission is impaired following DIDS, quinine and fluoxetine while the exocytotic release of glutamate-that is proposed to mediate synaptic transmission modulation by astrocytes-remains unaffected. In conclusion, our data provide evidence that the release of glutamate generating SICs occurs independently on exocytotic Ca(2+) -dependent glutamate release mechanism. |
