Channel-mediated release of glutamate from astrocytes via Bestrophin-1 potentiates synaptic strength

Title
Channel-mediated release of glutamate from astrocytes via Bestrophin-1 potentiates synaptic strength
Authors
한경석박형주서진수오수진윤보은조숙희우준성김혜연우동호Rolando BerlinguerGuido MannaioniStephen F. Traynelis최세영이창준
Issue Date
2011-11
Publisher
Society For Neuroscience
Abstract
Recent studies have revealed that astrocytes regulate neuronal activity by releasing excitatory amino acid such as glutamate in Ca2+ dependent manner. Although Ca2+-dependent vesicular glutamate release mechanism in astrocyte has been suggested, the mechanism of astrocytic glutamate release through a channel has not been directly tested yet. Here we report that hippocampal CA1 astrocytes display a novel glutamate release mechanism via large-anion-permeable Ca2+ activated anion channels (CAAC). We found that putative CAAC, Bestrophin-1 (Best1) is able to permeate glutamate in Ca2+ dependent manner. Using the agonist (TFLLR peptide) for glia-specific Gq-coupled receptor (PAR-1) in hippocampal CA1, we found that PAR-1 activation induces glutamate release through Best1 in Ca2+ dependent manner. To verify the function of astrocytic glutamate, we performed a detailed electrophysiological analysis from hippocampal slices using cell type specific lentiviral shRNA expression system to selectively knockdown astrocytic or neuronal Best1. We demonstrated that astrocytic Best1-mediated glutamate activates neuronal NMDARs and induces the potentiation of hippocampal synaptic activity by NMDAR-dependent manner.
URI
http://pubs.kist.re.kr/handle/201004/41174
Appears in Collections:
KIST Publication > Conference Paper
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