Channel-Mediated Tonic GABA Release from Glia

被引：436

作者：

Lee, Soojung ^{[1
]}

Yoon, Bo-Eun ^{[1
,2
,5
]}

Berglund, Ken ^{[3
]}

Oh, Soo-Jin ^{[1
,2
]}

Park, Hyungju ^{[1
]}

Shin, Hee-Sup ^{[1
,2
]}

Augustine, George J. ^{[2
,3
,4
]}

Lee, C. Justin ^{[1
,2
,5
]}

机构：

[1] Korea Inst Sci & Technol, Ctr Neural Sci, Seoul, South Korea

[2] Korea Inst Sci & Technol, Ctr Funct Connect, Seoul, South Korea

[3] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA

[4] Duke NUS Grad Med Sch, Program Neurosci & Behav Disorders, Singapore, Singapore

[5] Univ Sci & Technol, Neurosci Program, Taejon, South Korea

来源：

SCIENCE | 2010年 / 330卷 / 6005期

基金：

新加坡国家研究基金会;

关键词：

CEREBELLAR GRANULE CELLS; SYNAPTIC INHIBITION; RAT CEREBELLUM; ACTIVATION; ASTROCYTES; NEURONS; RECEPTORS; CHLORIDE; BRAIN; DEGENERATION;

D O I：

10.1126/science.1184334

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Synaptic inhibition is based on both tonic and phasic release of the inhibitory transmitter gamma-aminobutyric acid (GABA). Although phasic GABA release arises from Ca2+-dependent exocytosis from neurons, the mechanism of tonic GABA release is unclear. Here we report that tonic inhibition in the cerebellum is due to GABA being released from glial cells by permeation through the Bestrophin 1 (Best1) anion channel. We demonstrate that GABA directly permeates through Best1 to yield GABA release and that tonic inhibition is eliminated by silencing of Best1. Glial cells express both GABA and Best1, and selective expression of Best1 in glial cells, after preventing general expression of Best1, fully rescues tonic inhibition. Our results identify a molecular mechanism for tonic inhibition and establish a role for interactions between glia and neurons in mediating tonic inhibition.

引用

页码：790 / 796

页数：7

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