Channel-mediated tonic GABA release from glia
- Channel-mediated tonic GABA release from glia
- 윤보은; 이수정; Ken berglund; 오수진; 박형주; 신희섭; 조지어거스틴; 이창준
- tonic GABA; Glia; Bestrophin
- Issue Date
- Neuroscience 2010
- 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.
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- KIST Publication > Conference Paper
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