TREK-1 and Best1 Channels Mediate Fast and Slow Glutamate Release in Astrocytes upon GPCR Activation

Title
TREK-1 and Best1 Channels Mediate Fast and Slow Glutamate Release in Astrocytes upon GPCR Activation
Authors
우동호한경석심재완윤보은김은주Bae, Jin Young오수진황은미Marmorstein, Alan D.Bae, Yong ChulPark, Jae-Yong이창준
Issue Date
2012-09
Publisher
Cell
Citation
VOL 151, NO 1, 25-40
Abstract
Astrocytes release glutamate upon activation of various GPCRs to exert important roles in synaptic functions. However, the molecular mechanism of release has been controversial. Here, we report two kinetically distinct modes of nonvesicular, channelmediated glutamate release. The fast mode requires activation of Gαi, dissociation of Gβγ, and subsequent opening of glutamate-permeable, two-pore domain potassium channel TREK-1 through direct interaction between Gβγ and N terminus of TREK-1. The slow mode is Ca2+ dependent and requires Gαq activation and opening of glutamate-permeable, Ca2+-activated anion channel Best1. Ultrastructural analyses demonstrate that TREK-1 is preferentially localized at cell body and processes, whereas Best1 is mostly found in microdomains of astrocytes near synapses. Diffusion modeling predicts that the fast mode can target neuronal mGluR with peak glutamate concentration of 100 μM, whereas slow mode targets neuronal NMDA receptors at around 1 μM. Our results reveal two distinct sources of astrocytic glutamate that can differentially influence neighboring neurons.
URI
http://pubs.kist.re.kr/handle/201004/43233
ISSN
00928674
Appears in Collections:
KIST Publication > Article
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE