Lee, Soojung Yoon, Bo-Eun Berglund, Ken Oh, Soo-Jin Park, Hyungju Shin, Hee-Sup Augustine, George J. Lee, C. Justin 2024-01-20T18:04:58Z 2024-01-20T18:04:58Z 2021-09-05 2010-11 0036-8075 https://pubs.kist.re.kr/handle/201004/130942 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. English American Association for the Advancement of Science Channel-Mediated Tonic GABA Release from Glia Article 10.1126/science.1184334 1 Science, v.330, no.6005, pp.790 - 796 Science 330 6005 790 796 N scie scopus 000283855700035 2-s2.0-77958454583 Multidisciplinary Sciences Science & Technology - Other Topics Article CEREBELLAR GRANULE CELLS SYNAPTIC INHIBITION RAT CEREBELLUM ACTIVATION ASTROCYTES NEURONS RECEPTORS CHLORIDE BRAIN DEGENERATION bestrophin calcium anion Bergmann glia lamellar astrocyte cerebellum granule cell