Channel-mediated tonic GABA release from glia

Title
Channel-mediated tonic GABA release from glia
Authors
윤보은이수정Ken berglund오수진박형주신희섭조지어거스틴이창준
Keywords
tonic GABA; Glia; Bestrophin
Issue Date
2010-11
Publisher
Neuroscience 2010
Abstract
Synaptic inhibition is based on both tonic and phasic release of the inhibitory transmitter, GABA. While phasic GABA release arises from conventional, Ca2+- dependent exocytosis from neurons, the mechanism and source of tonic GABA release are 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. By developing and utilizing a two-cell biosensor technique, we demonstrate that GABA can directly permeate through Best1 to yield GABA release. Tonic inhibition is eliminated by various drugs that block Best1 and by selective RNA-based silencing of Best1 expression. We confirmed that glial cells express both GABA and Best1 by immunohistochemistry. We found that selective expression of Best1 in glial cells, after preventing general expression of Best1, fully rescues tonic inhibition. Therefore, we conclude that Best1-mediated GABA release from glial cells is responsible for tonic inhibition in the cerebellum. Our results identify a molecular mechanism for tonic inhibition and establish a novel role for neuron-glial interactions in regulating brain function.
URI
http://pubs.kist.re.kr/handle/201004/38900
Appears in Collections:
KIST Publication > Conference Paper
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