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Molecular Brain
Published in: Molecular Brain 1/2013

Open Access 01-12-2013 | Research

Channel-mediated astrocytic glutamate release via Bestrophin-1 targets synaptic NMDARs

Authors: Kyung-Seok Han, Junsung Woo, Hyungju Park, Bong-June Yoon, Sukwoo Choi, C Justin Lee

Published in: Molecular Brain | Issue 1/2013

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Abstract

Background

Astrocytes regulate neuronal excitability and synaptic activity by releasing gliotransmitters such as glutamate. Our recent study demonstrated that astrocytes release glutamate upon GPCR activation via Ca2+ activated anion channel, Bestrophin-1 (Best1). The target of Best1-mediated astrocytic glutamate has been shown to be the neuronal NMDA receptors (NMDAR). However, whether it targets synaptically or extra-synaptically localized NMDAR is not known.

Findings

We recorded spontaneous miniature excitatory postsynaptic currents (mEPSCs) from CA1 pyramidal cells to test whether Best1-mediated astrocytic glutamate targets synaptic NMDAR. An agonist of protease activated receptor 1 (PAR1) was used to induce astrocytic Ca2+ increase and glutamate release. Firstly, we found that activation of PAR1 and subsequent release of glutamate from astrocyte does not alone increase the frequency of mEPSCs. Secondly, we found that mEPSC rise time is variable depending on the different electrotonic distances from the somatic recording site to the synaptic region where each mEPSC occurs. Two subgroups of mEPSC from CA1 pyramidal neuron by rise time were selected and analyzed. One group is fast rising mEPSCs with a rise time of 1 ~ 5 ms, representing synaptic activities arising from proximal dendrites. The other group is slowly rising mEPSCs with a rise time of 5 ~ 10 ms, representing synaptic events arising from glutamate release at synapses located in the distal dendrites. We used cell-type specific Best1 gene silencing system by Cre-loxP cleavage to dissociate the effect of neuronal and astrocytic Best1. Astrocytic Best1-mediated glutamate release by PAR1 activation did not affect decay kinetics, frequency, and amplitude of fast rising mEPSC. In contrast, PAR1 activation resulted in an NMDA receptor component to be present on slowly rising mEPSC, but did not alter frequency or amplitude.

Conclusions

Our results indicate that astrocytic glutamate via Best1 channel targets and activates synaptic NMDARs.
Appendix
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Metadata
Title
Channel-mediated astrocytic glutamate release via Bestrophin-1 targets synaptic NMDARs
Authors
Kyung-Seok Han
Junsung Woo
Hyungju Park
Bong-June Yoon
Sukwoo Choi
C Justin Lee
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Molecular Brain / Issue 1/2013
Electronic ISSN: 1756-6606
DOI
https://doi.org/10.1186/1756-6606-6-4

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