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  Benzodiazepine-induced motor impairment linked to point mutation in cerebeilar GABAA receptor

Korpi, E. R., Kleingoor, C., Kettenmann, H., & Seeburg, P. H. (1993). Benzodiazepine-induced motor impairment linked to point mutation in cerebeilar GABAA receptor. Nature, 361, 356-359. doi:10.1038/361356a0.

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Genre: Journal Article
Alternative Title : Natural point mutation reveals a behavioural correlate for a cerebellar GABAA receptor

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Nature_361_1993_356.pdf (Any fulltext), 495KB
 
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Korpi, Esa R., Author
Kleingoor, Claudia, Author
Kettenmann, Helmut, Author
Seeburg, Peter H.1, Author              
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1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              

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 Abstract: THE selectively outbred alcohol-non-tolerant (ANT) rat line1 is highly susceptible to impairment of postural reflexes by benzodiazepine agonists2 such as diazepam. ANT cerebella are generally devoid3 of diazepam-insensitive high-affinity binding of the benzodiazepine [3H]Ro 15-4513 (refs 4, 5), whereas in non-selected strains such binding marks a granule-cell-specific GABAA (γ-aminobutyric acid) receptor containing the α6 subunit5,6. A critical determinant for diazepam insensitivity of this ‘wild-type’ cerebeilar GABAA receptor is an arginine residue7 in α6 position 100, where other a subunits carry a histidine8. Here we report that the ct6 gene of ANT rats is expressed at wild-type levels but carries a point mutation generating an arginine-to-glutamine substitution at position 100. In consequence, α6(Q 100)β2γ2 receptors show diazepam-mediated potentiation of GABA-activated currents and diazepam-sensitive binding of [3H]Rol5-4513. Our results suggest that cerebeilar motor control may be a distinct behavioural correlate of the a6-subunit-containing GABAA receptor subtype.

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Language(s): eng - English
 Dates: 1992-08-191992-12-081993-01-28
 Publication Status: Published in print
 Pages: 4
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 666821
DOI: 10.1038/361356a0
Other: 4003
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Title: Nature
  Abbreviation : Nature
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 361 Sequence Number: - Start / End Page: 356 - 359 Identifier: ISSN: 0028-0836
CoNE: https://pure.mpg.de/cone/journals/resource/954925427238