Preferential coassembly of alpha 4 and delta subunits of the gamma-aminobutyric acid(A) receptor in rat thalamus

Pharmacological study of rat thalamic gamma-aminobutyric acid, (GABA(A)) re ceptors revealed the presence of two distinct populations, namely, diazepam -sensitive and diazepam-insensitive [H-3]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 sit es exhibited a pharmacology that was distinct from diazepam-sensitive sites but comparable to that of the alpha 4 beta 3 gamma 2 subtype of the GABA(A ) receptor stably expressed in L(tk(-)) cells. Immunoprecipitation experime nts with a specific anti-alpha 4-antiserum immunoprecipitated 20 and 7% of total thalamic [H-3]muscimol and [H-3]Ro15-4513 sites, respectively. Combin atorial immunoprecipitation using antisera against the alpha 4,gamma 2, and delta subunit revealed that alpha 4 delta- and alpha 4 gamma 2-containing receptors account for 13 +/- 2 and 8 +/- 3% of [H-3]muscimol sites from tha lamus, respectively. It also indicated that all delta subunits coexist with an alpha 4 subunit in this brain region. In conclusion, our results show t hat: in rat thalamus both alpha 4 beta gamma 2 and alpha 4 beta delta subty pes are expressed but alpha 4 beta delta is the major alpha 4-containing GA BA(A) receptor population.