gamma-Aminobutyric acidA receptors displaying association of gamma 3-subunits with beta 2/3 and different alpha-subunits exhibit unique pharmacological properties.

Abstract Two polyclonal antibodies were raised against the gamma 3-subunit of gamma-aminobutyric acidA (GABAA) receptors. These antibodies were able to precipitate GABAA receptors from brain membrane extracts, and the precipitated receptors exhibited benzodiazepine binding properties that were dramatically different from those of receptors precipitated by anti-gamma 2 antibodies. The anti-gamma 3 antibodies were used for immunopurification of GABAA receptors containing gamma 3-subunits. Western blot analysis of the immunopurified GABAA receptors indicated that the gamma 3-subunit exhibits an apparent molecular mass of 43-46 kDa. Furthermore, in addition to gamma 3-subunits, beta 2/3-, alpha 1-, alpha 2-, alpha 3-, alpha 4-, and alpha 6-subunits could be detected in immunoaffinity column eluates from total brain and cerebellum, respectively. These data indicate that gamma 3-subunits can combine with most alpha-subunits to form a multiplicity of GABAA receptors with distinct pharmacology.