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GABAA/Benzodiazepine receptors in acutely isolated hippocampal astrocytes

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Item Type:Article
Title:GABAA/Benzodiazepine receptors in acutely isolated hippocampal astrocytes
Creators Name:Fraser, D.D. and Duffy, S. and Angelidis, K.J. and Perezvelazquez, J.L. and Kettenmann, H. and MacVicar, B.A.
Abstract:The properties of GABA receptor-mediated responses were examined in noncultured astrocytes, acutely isolated from the mature rat hippocampus. Whole-cell patch clamping revealed a GABA-activated Cl- conductance that was mimicked by the GABAA receptor agonist muscimol and depressed by the GABAA antagonists bicuculline and picrotoxin. The GABAA-activated currents were potentiated by the barbiturate pentobarbital and the benzodiazepine diazepam. The benzodiazepine inverse agonist DMCM either enhanced or depressed the astrocytic GABAA-mediated responses, suggesting receptor heterogeneity with respect to pharmacologic profiles. In addition, GABA evoked an increase in [Ca2+]n measured by indo-1 fluorometry, which was depressed in the presence of verapamil or picrotoxin. A GABAA-induced depolarization, therefore, causes Ca2+ influx through voltage-gated Ca2+ channels. The expression and subcellular localization of GABAA receptors and its subunits were examined using immunohistochemical and fluorescent benzodiazepine binding techniques. Polyclonal antisera raised against the GABAA/benzodiazepine receptor, which recognizes multiple subunit isoforms, labeled receptors on the astrocytic cell body and most large processes. In contrast, antisera generated against either alpha 1 or beta 1 subunit peptides revealed immunoreactivity predominantly on a subset of processes. To determine the subcellular distribution of membrane-bound receptors, a fluorescent benzodiazepine derivative was superfused over live astrocytes and visualized with laser-scanning confocal microscopy. Specific fluorescence was distributed in discrete clusters on the cell soma and a subset of distal processes. Collectively, these data support the view that astrocytes, like neurons, express GABAA receptors and target subunit isoforms to distinct cellular localizations. Astrocytic GABAA receptors may be involved in both [Cl-]o and [pH]o homeostasis, and a GABA-evoked increase in [Ca2+]i could serve as a signal between GABAergic neurons and astrocytes.
Keywords:Astrocyte, GABA Receptor, Cl- Current, Benzodiazepines, Barbiturates, Voltage-Activated Ca2+ Influx, Western Blot, Immunocytochemistry, Ligand Binding, Animals, Rats
Source:Journal of Neuroscience
ISSN:0270-6474
Publisher:Society for Neuroscience (U.S.A.)
Volume:15
Number:4
Page Range:2720-2732
Date:April 1995
Additional Information:Copyright (c) 1995 by The Society for Neuroscience
Official Publication:http://www.jneurosci.org/cgi/content/abstract/15/4/2720
PubMed:View item in PubMed

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