Molecular heterogeneity of the type I GABAA/benzodiazepine receptor complex

We have investigated the presence of alpha 1, gamma 2 and beta 2-3 subunits as part of the type I (high affinity for [3H]zolpidem) GABAA/benzodiazepine receptor from rat cerebral cortex. Three subunit specific antibodies have been used (anti-alpha 1, to the C-terminal of rat alpha 1 subunit; anti-gamma 2, to the large intracellular loop of the gamma 2 subunit short form and the monoclonal 62-3G1, specific to beta 2-3 subunits) in immunoprecipitation experiments of the [3H]zolpidem binding activity or the 51,000 Da [3H]Ro 15-4513 photoaffinity labeled peptide (P51). The results indicated that alpha 1 subunit was present in the whole population (90%) of the GABAA/benzodiazepine receptors with high affinity for [3H]zolpidem. We cannot exclude the presence of other alpha subunits co-localized with alpha 1. On the one hand, 70-75% of type I GABAA/benzodiazepine receptor from rat cortex have co-existing alpha 1, beta 2-3 and gamma 2 subunits. We call this type Ia. On the other hand, 20-25% of the type I GABAA/benzodiazepine receptor complex should be constructed by the association of alpha 1 with subunits other than beta 2-3 and gamma 2. We call this type Ib. The identity of these subunits is currently unknown.