期刊
JOURNAL OF NEUROSCIENCE
卷 20, 期 2, 页码 666-673出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.20-02-00666.2000
关键词
astrocyte-neuron signaling; astrocyte calcium waves; transmitter release; Botulinum neurotoxin; bafilomycin; exocytosis; SNARE protein; V-ATPase
资金
- NINDS NIH HHS [NS37585, NS24233] Funding Source: Medline
We investigated the cellular mechanisms underlying the Ca2+ dependent release of glutamate from cultured astrocytes isolated from rat hippocampus. Using Ca2+ imaging and electrophysiological techniques, we analyzed the effects of disrupting astrocytic vesicle proteins on the ability of astrocytes to release glutamate and to cause neuronal electrophysiological responses, i.e., a slow inward current (SIC) and/or an increase in the frequency of miniature synaptic currents. We found that the Ca2+-dependent glutamate release from astrocytes is not caused by the reverse operation of glutamate transporters, because the astrocyte-induced glutamate-mediated responses in neurons were affected neither by inhibitors of glutamate transporters (beta-threo-hydroxyaspartate, dihydrokainate, and L-trans-pyrrolidine-2,4-dicarboxylate) nor by replacement of extracellular sodium with lithium. We show that Ca2+-dependent glutamate release from astrocytes requires an electrochemical gradient necessary for glutamate uptake in vesicles, because bafilomycin A(1), a vacuolar-type H+-ATPase inhibitor, reduced glutamate release from astrocytes. Injection of astrocytes with the light chain of the neurotoxin Botulinum B that selectively cleaves the vesicle-associated SNARE protein synaptobrevin inhibited the astrocyte-induced glutamate response in neurons. Therefore, the Ca2+-dependent glutamate release from astrocytes is a SNARE protein-dependent process that requires the presence of functional vesicle-associated proteins, suggesting that astrocytes store glutamate in vesicles and that it is released through an exocytotic pathway.
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