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The α 1 and α 6 Subunits Can Coexist in the Same Cerebellar GABA A Receptor Maintaining Their Individual Benzodiazepine‐Binding Specificities
Author(s) -
Khan Zafar U.,
Gutiérrez Antonia,
De Blas Angel L.
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.66020685.x
Subject(s) - gabaa receptor , flumazenil , cys loop receptors , receptor , interleukin 5 receptor alpha subunit , interleukin 10 receptor, alpha subunit , g alpha subunit , alpha (finance) , gabaa rho receptor , muscimol , protein subunit , chemistry , biology , biochemistry , medicine , acetylcholine receptor , construct validity , nursing , nicotinic acetylcholine receptor , patient satisfaction , gene
Two GABA A receptor subunit‐specific antibodies anti‐α 6 and anti‐α 1 have been used for elucidating the relationship between the presence of α 1 and/or α 6 subunits in the cerebellar GABA A receptors and the benzodiazepine‐binding specificity. Receptor immunoprecipitation with the subunit‐specific antibodies shows that 39% of the cerebellar GABA A receptors have α 6 , whereas 76% of the receptors have α 1 as determined by [ 3 H]muscimol binding. Results show that 42–45% of the receptors having α 6 also have α 1 , whereas 13–15% of the receptors that contain α 1 also have α 6 . The immunoprecipitation results as well as immunopurification and immunoblotting experiments reveal the existence of three types of cerebellar GABA A receptors; i.e., one has both α 1 and α 6 subunits, a second type has α 1 but not α 6 , and a third type has α 6 but not α 1 subunits. The results also show that receptors where α 1 and α 6 subunits coexist have two pharmacologically different benzodiazepine‐binding properties, each associated with a different α subunit. The α 1 subunit contributes the high‐affinity binding of [ 3 H]Ro 15‐1788 (flumazenil) and the diazepam‐sensitive binding of [ 3 H]Ro 15‐4513. The α 6 subunit contributes the diazepam‐insensitive binding of [ 3 H]Ro 15‐4513, but it does not bind [ 3 H]Ro 15‐1788 with high affinity. Thus, in the cerebellar α 1 –α 6 GABA A receptors, there is no dominance of the pharmacology of one α subunit over the other.