Quantitative characterization of alpha 6 and alpha 1 alpha 6 subunit-containing native gamma-aminobutyric acidA receptors of adult rat cerebellum demonstrates two alpha subunits per receptor oligomer

J Biol Chem. 1995 Sep 8;270(36):21285-90. doi: 10.1074/jbc.270.36.21285.

Abstract

gamma-Aminobutyric acidA (GABAA) receptors were purified from adult rat cerebella by anti-alpha 6(1-16 Cys) antibody affinity chromatography. Immunoblots of the alpha 6 subunit-containing receptors showed the copurification of the alpha 1, beta 2/3, gamma 2, delta but not alpha 2 and alpha 3 GABAA receptor polypeptides. Further fractionation of this receptor subpopulation by anti-GABAA receptor subunit alpha 6(1-16 Cys) and anti-alpha 1(413-429) antibody affinity columns in series substantiated the coassociation of the alpha 1 and alpha 6 polypeptides. The percentage of coexistence of the two subunits was determined by quantitative immunoblotting, which found that 41 +/- 12% of alpha 6 subunit immunoreactivity is associated with the alpha 1 subunit. The ratios of the alpha 1:alpha 6 subunits in the double purified receptor preparations was found to be 1:1, thus determining directly for the first time subunit ratios within native GABAA receptors. The benzodiazepine pharmacology of the alpha 1 alpha 6 subunit-containing receptors was shown to be predominantly benzodiazepine-insensitive by quantitative immunoprecipitation assays. These results are the first direct quantitative studies of subunit ratios within a population of native GABAA receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Benzodiazepines / pharmacology
  • Biopolymers
  • Blotting, Western
  • Cattle
  • Cerebellum / metabolism*
  • Chromatography, Affinity / methods
  • Immunoglobulin Fab Fragments
  • Molecular Sequence Data
  • Precipitin Tests
  • Rats
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / isolation & purification
  • Receptors, GABA-A / metabolism*

Substances

  • Biopolymers
  • Immunoglobulin Fab Fragments
  • Receptors, GABA-A
  • Benzodiazepines