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• W2888140834 startingPage "2188" @default.
• W2888140834 abstract "Abstract 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." @default.
• W2888140834 created "2018-08-31" @default.
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• W2888140834 date "2018-08-25" @default.
• W2888140834 modified "2023-10-16" @default.
• W2888140834 title "Insights into the release mechanism of astrocytic glutamate evoking in neurons NMDA receptor‐mediated slow depolarizing inward currents" @default.
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• W2888140834 doi "https://doi.org/10.1002/glia.23473" @default.
• W2888140834 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30144319" @default.
• W2888140834 hasPublicationYear "2018" @default.
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