期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2014
卷号：111
期号：49
页码：17522-17527
DOI：10.1073/pnas.1419632111
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceEarly postnatal development of the cerebellum involves a number of events that require signaling via the neurotransmitter GABA, which acts on specific receptors anchored in the plasma membrane. GABAergic transmission regulates the proliferation and migration of neuronal precursors of astrocytic lineage. Glial cells are known to express GABA-A receptors that include GABA{rho} subunits, but their expression pattern, functional properties, and trafficking dynamics remain unknown. This study found that a large number of glial cells express GABA{rho} in the cerebellum. Functional properties and intracellular trafficking of GABA-A receptors in glial cells grown in vitro suggest a different mechanism of GABAergic control of extrasynaptic transmission. GABA-A receptors mediating synaptic or extrasynaptic transmission are molecularly and functionally distinct, and glial cells are known to express a plethora of GABA-A subunits. Here we demonstrate that GFAP+ cells of the granular layer of cerebellum express GABA{rho} subunits during early postnatal development, thereby conferring peculiar pharmacologic characteristics to GABA responses. Electron microscopy revealed the presence of GABA{rho} in the plasma membrane of GFAP+ cells. In contrast, expression in the adult was restricted to Purkinje neurons and a subset of ependymal cells. Electrophysiological studies in vitro revealed that astrocytes express functional receptors with an EC50 of 52.2 {+/-} 11.8 M for GABA. The evoked currents were inhibited by bicuculline (100 M) and TPMPA (IC50, 5.9 {+/-} 0.6 M), indicating the presence of a GABA{rho} component. Coimmunoprecipitation demonstrated protein-protein interactions between GABA{rho}1 and GABA1, and double immunofluorescence showed that these subunits colocalize in the plasma membrane. Three populations of GABA-A receptors in astrocytes were identified: classic GABA-A, bicuculline-insensitive GABA{rho
