PMID- 7678923
OWN - NLM
STAT- MEDLINE
DCOM- 19930302
LR  - 20131121
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 361
IP  - 6410
DP  - 1993 Jan 28
TI  - Benzodiazepine-induced motor impairment linked to point mutation in cerebellar 
      GABAA receptor.
PG  - 356-9
AB  - 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.
FAU - Korpi, E R
AU  - Korpi ER
AD  - Laboratory of Molecular Neuroendocrinology, University of Heidelberg, Germany.
FAU - Kleingoor, C
AU  - Kleingoor C
FAU - Kettenmann, H
AU  - Kettenmann H
FAU - Seeburg, P H
AU  - Seeburg PH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Affinity Labels)
RN  - 0 (Azides)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, GABA-A)
RN  - 10028-17-8 (Tritium)
RN  - 12794-10-4 (Benzodiazepines)
RN  - 24937-83-5 (Poly A)
RN  - 3K9958V90M (Ethanol)
RN  - 4QD397987E (Histidine)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 63231-63-0 (RNA)
RN  - 91917-65-6 (Ro 15-4513)
RN  - 94ZLA3W45F (Arginine)
RN  - Q3JTX2Q7TU (Diazepam)
SB  - IM
CIN - Nature. 1993 Jan 28;361(6410):302-3. PMID: 7678921
MH  - Affinity Labels/metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - *Arginine
MH  - Autoradiography
MH  - Azides/metabolism
MH  - Base Sequence
MH  - Benzodiazepines/metabolism
MH  - Binding, Competitive
MH  - Cerebellum/*physiology
MH  - Diazepam/*pharmacology
MH  - Drug Tolerance/genetics
MH  - Ethanol/*pharmacology
MH  - *Histidine
MH  - In Situ Hybridization
MH  - Kinetics
MH  - Macromolecular Substances
MH  - Models, Structural
MH  - Molecular Sequence Data
MH  - Motor Activity/*drug effects
MH  - Oligodeoxyribonucleotides
MH  - *Point Mutation
MH  - Poly A/genetics/isolation & purification
MH  - Protein Structure, Secondary
MH  - RNA/genetics/isolation & purification
MH  - RNA, Messenger/analysis/genetics/*metabolism
MH  - Rats
MH  - Rats, Mutant Strains
MH  - Receptors, GABA-A/chemistry/*genetics/physiology
MH  - Tritium
MH  - gamma-Aminobutyric Acid/*pharmacology
EDAT- 1993/01/28 00:00
MHDA- 1993/01/28 00:01
CRDT- 1993/01/28 00:00
PHST- 1993/01/28 00:00 [pubmed]
PHST- 1993/01/28 00:01 [medline]
PHST- 1993/01/28 00:00 [entrez]
AID - 10.1038/361356a0 [doi]
PST - ppublish
SO  - Nature. 1993 Jan 28;361(6410):356-9. doi: 10.1038/361356a0.