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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6410
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pubmed:dateCreated |
1993-3-2
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pubmed:abstractText |
The selectively outbred alcohol-non-tolerant (ANT) rat line is highly susceptible to impairment of postural reflexes by benzodiazepine agonists such as diazepam. ANT cerebella are generally devoid of diazepam-insensitive high-affinity binding of the benzodiazepine [3H]Ro15-4513, whereas in non-selected strains such binding marks a granule-cell-specific GABAA (gamma-aminobutyric acid) receptor containing the alpha 6 subunit. A critical determinant for diazepam insensitivity of this 'wild-type' cerebellar GABAA receptor is an arginine residue in alpha 6 position 100, where other alpha subunits carry a histidine. Here we report that the alpha 6 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, alpha 6(Q100)beta 2 gamma 2 receptors show diazepam-mediated potentiation of GABA-activated currents and diazepam-sensitive binding of [3H]Ro15-4513. Our results suggest that cerebellar motor control may be a distinct behavioural correlate of the alpha 6-subunit-containing GABAA receptor subtype.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Affinity Labels,
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/Azides,
http://linkedlifedata.com/resource/pubmed/chemical/Benzodiazepines,
http://linkedlifedata.com/resource/pubmed/chemical/Diazepam,
http://linkedlifedata.com/resource/pubmed/chemical/Ethanol,
http://linkedlifedata.com/resource/pubmed/chemical/Histidine,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Poly A,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, GABA-A,
http://linkedlifedata.com/resource/pubmed/chemical/Ro 15-4513,
http://linkedlifedata.com/resource/pubmed/chemical/Tritium,
http://linkedlifedata.com/resource/pubmed/chemical/gamma-Aminobutyric Acid
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0028-0836
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
28
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pubmed:volume |
361
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
356-9
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:7678923-Affinity Labels,
pubmed-meshheading:7678923-Amino Acid Sequence,
pubmed-meshheading:7678923-Animals,
pubmed-meshheading:7678923-Arginine,
pubmed-meshheading:7678923-Autoradiography,
pubmed-meshheading:7678923-Azides,
pubmed-meshheading:7678923-Base Sequence,
pubmed-meshheading:7678923-Benzodiazepines,
pubmed-meshheading:7678923-Binding, Competitive,
pubmed-meshheading:7678923-Cerebellum,
pubmed-meshheading:7678923-Diazepam,
pubmed-meshheading:7678923-Drug Tolerance,
pubmed-meshheading:7678923-Ethanol,
pubmed-meshheading:7678923-Histidine,
pubmed-meshheading:7678923-In Situ Hybridization,
pubmed-meshheading:7678923-Kinetics,
pubmed-meshheading:7678923-Macromolecular Substances,
pubmed-meshheading:7678923-Models, Structural,
pubmed-meshheading:7678923-Molecular Sequence Data,
pubmed-meshheading:7678923-Motor Activity,
pubmed-meshheading:7678923-Oligodeoxyribonucleotides,
pubmed-meshheading:7678923-Point Mutation,
pubmed-meshheading:7678923-Poly A,
pubmed-meshheading:7678923-Protein Structure, Secondary,
pubmed-meshheading:7678923-RNA,
pubmed-meshheading:7678923-RNA, Messenger,
pubmed-meshheading:7678923-Rats,
pubmed-meshheading:7678923-Rats, Mutant Strains,
pubmed-meshheading:7678923-Receptors, GABA-A,
pubmed-meshheading:7678923-Tritium,
pubmed-meshheading:7678923-gamma-Aminobutyric Acid
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pubmed:year |
1993
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pubmed:articleTitle |
Benzodiazepine-induced motor impairment linked to point mutation in cerebellar GABAA receptor.
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pubmed:affiliation |
Laboratory of Molecular Neuroendocrinology, University of Heidelberg, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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