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Science 330 (6005): 790-796

Copyright © 2010 by the American Association for the Advancement of Science

Channel-Mediated Tonic GABA Release from Glia

Soojung Lee,1,* Bo-Eun Yoon,1,2,5,* Ken Berglund,3 Soo-Jin Oh,1,2 Hyungju Park,1 Hee-Sup Shin,1,2 George J. Augustine,2,3,4 C. Justin Lee1,2,5,{dagger}

Abstract: 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.

1 Center for Neural Science, Korea Institute of Science and Technology (KIST), Seoul, Korea.
2 Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, Korea.
3 Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
4 Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore.
5 Neuroscience Program, University of Science and Technology (UST), Daejeon, Korea.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: cjl{at}kist.re.kr


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