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TY - JOUR AU - Lüddens, Hartmut AU - Pritchett, Dolan B. AU - Köhler, Martin AU - Killisch, Iris AU - Keinänen, Kari AU - Monyer, Hannah AU - Sprengel, Rolf AU - Seeburg, Peter H. PY - 1990 DA - 1990/08/01 TI - Cerebellar GABAA receptor selective for a behavioural alcohol antagonist JO - Nature SP - 648 EP - 651 VL - 346 IS - 6285 AB - BENZODIAZEPINES are widely prescribed anxiolytics and anti-convulsants which bind with high affinity to sites on the GABAA receptor/Cl– channel complex and potentiate the effect of the neurotransmitter GABA (γ-aminobutyric acid)1,2. The heterogeneity of benzodiazepine recognition sites in the central nervous system1,3,4 was revealed by studies showing different classes of GABAA receptor subunits (classes α, β and γ)5–7 and variant subunits in these classes, particularly in the α-class8–11. Expression of recombinant subunits produces functional receptors; when certain α-variants are coexpressed with β- and γ-subunits the resulting receptors have pharmacological properties characteristic of GABAA–benzodiazepine type I or type II receptors6,11,12. The α-variants are differentially expressed in the central nervous system13 and can be photoaffinity-labelled with benzodiazepines1,14,15. Here we report a novel α-subunit (α6) of cerebellar granule cells. We show that recombinant receptors composed of α6, β2 and γ2 subunits bind with high affinity to the GABA agonist [3H]muscimol and the benzodiazepine [3H]Rol5-4513 (refs 14,16) but not the other benzodiazepines or β-carbolines. The same distinctive pharmacology is observed with GABAA receptors from rat cerebellum immunoprecipitated by an antiserum specific for the α6 subunit. We conclude that this α-subunit is part of a cerebellar receptor subtype, selective for Rol5-4513 (ref. 17), an antagonist of alcohol-induced motor incoordination and ataxia18. SN - 1476-4687 UR - https://doi.org/10.1038/346648a0 DO - 10.1038/346648a0 ID - Lüddens1990 ER -