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  GABA A -receptors: Structural requirements and sites of gene expression in mammalian brain

Möhler, H., Malherbe, P., Draguhn, A., & Richards, J. G. (1990). GABA A -receptors: Structural requirements and sites of gene expression in mammalian brain. Neurochemical Research, 15(2), 199-207. doi:10.1007/BF00972210.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0019-ACDE-D Version Permalink: http://hdl.handle.net/21.11116/0000-0000-7377-9
Genre: Journal Article

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NeurochemRes_15_1990_199.pdf (Any fulltext), 2MB
 
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 Creators:
Möhler, H., Author
Malherbe, P., Author
Draguhn, Andreas1, Author              
Richards, J. G., Author
Affiliations:
1Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497701              

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Free keywords: In situ hybridization; GABAA-receptor subunits; GABAA-receptor heterogeneity; Xenopus oocytes; diazepam
 Abstract: GABAA-receptors, the major synaptic targets for the neutotransmitter GABA, are gated chloride channels. By their allosteric drug-induced modulation they serve as molecular control elements through which the levels of anxiety, vigilance, muscle tension and epileptiform activity can be regulated. Despite their functional prominence, the structural requirements of fully functional GABAA-receptors are still elusive. Expression of cDNAs coding for the α1- and β1-subunits of rat brain yielded GABA-gated chloride channels which were modulated by barbiturates but displayed only agonistic responses to ligands of the benzodiazepine receptor. GABAA-receptors with fully functional benzodiazepine receptor sites were formed when the α1- and α1-subunits were coexpressed with the γ2-subunit of rat brain. These receptors, however, failed to show cooperativity of GABA in gating the channel. In order to determine the subunit repertoire available for receptor assembly in different neuronal populations in vivo, the sites of subunit gene expression were (α1, α2, α3, α5, α6, β1, β2, β3, γ2) mapped by in situ hybridization histochemistry in brain sections. The mRNAs of the α1-, β1- and γ2-subunits were co-localized e.g. in mitral cells of olfactory bulb, pyramidal cells of hippocampus as well as granule cells of dentate gyrus and cerebellum. The lack of colocalization in various other brain areas points to an extensive receptor heterogeneity. The presence of multiple GABAA-receptors in brain may contribute to synaptic plasticity, differential responsiveness of neurons to GABA and to variations in drug profiles.

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Language(s): eng - English
 Dates: 19891989-10-231990-02
 Publication Status: Published in print
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1007/BF00972210
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Title: Neurochemical Research
  Other : Neurochem. Res.
Source Genre: Journal
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Publ. Info: New York : Kluwer Academic/Plenum Publishers [etc.]
Pages: - Volume / Issue: 15 (2) Sequence Number: - Start / End Page: 199 - 207 Identifier: ISSN: 0364-3190
CoNE: https://pure.mpg.de/cone/journals/resource/954925523746