Preferential Coassembly of α4 and δ Subunits of the γ-Aminobutyric AcidAReceptor in Rat Thalamus

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Abstract
Pharmacological study of rat thalamic γ-aminobutyric acidA (GABAA) receptors revealed the presence of two distinct populations, namely, diazepam-sensitive and diazepam-insensitive [3H]Ro15–4513 binding sites accounting for 94 ± 2% (1339 ± 253 fmol/mg protein) and 6 ± 2% (90 ± 44 fmol/mg protein) of total sites, respectively. Thalamic diazepam-insensitive sites exhibited a pharmacology that was distinct from diazepam-sensitive sites but comparable to that of the α4β3γ2 subtype of the GABAAreceptor stably expressed in L(tk-) cells. Immunoprecipitation experiments with a specific anti-α4-antiserum immunoprecipitated 20 and 7% of total thalamic [3H]muscimol and [3H]Ro15–4513 sites, respectively. Combinatorial immunoprecipitation using antisera against the α4, γ2, and δ subunit revealed that α4δ- and α4γ2-containing receptors account for 13 ± 2 and 8 ± 3% of [3H]muscimol sites from thalamus, respectively. It also indicated that all δ subunits coexist with an α4 subunit in this brain region. In conclusion, our results show that in rat thalamus both α4βγ2 and α4βδ subtypes are expressed but α4βδ is the major α4-containing GABAA receptor population.