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GABA(A) receptors are chloride channels composed of five subunits. Cerebellar granule cells express abundantly six subunits belonging to four subunit classes. These are assembled into a number of distinct receptors, but the regulation of their relative proportions is yet unknown. Here, we studied the composition of cerebellar GABA(A) receptors after targeted disruption of the delta subunit gene. In membranes and extracts of delta-/- cerebellum, [(3)H]muscimol binding was not significantly changed, whereas [(3)H]Ro15-4513 binding was increased by 52% due to an increase in diazepam-insensitive binding. Immunocytochemical and Western blot analysis revealed no change in alpha(6) subunits but an increased expression of gamma(2) subunits in delta-/- cerebellum. Immunoaffinity chromatography of cerebellar extracts indicated there was an increased coassembly of alpha(6) and gamma(2) subunits and that 24% of all receptors in delta-/- cerebellum did not contain a gamma subunit. Because 97% of delta subunits are coassembled with alpha(6) subunits in the cerebellum of wild-type mice, these results indicated that, in delta-/- mice, alpha(6)betagamma(2) and alphabeta receptors replaced delta subunit-containing receptors. The availability of the delta subunit, thus, influences the level of expression or the extent of assembly of the gamma(2) subunit, although these two subunits do not occur in the same receptor.

Original publication

DOI

10.1074/jbc.M011054200

Type

Journal article

Journal

J biol chem

Publication Date

30/03/2001

Volume

276

Pages

10532 - 10538

Keywords

Animals, Blotting, Western, Cell Membrane, Cerebellum, Diazepam, Electrophoresis, Polyacrylamide Gel, Immunoblotting, Immunohistochemistry, Kinetics, Mice, Mice, Transgenic, Mutagenesis, Site-Directed, Mutation, Precipitin Tests, Protein Binding, Receptors, GABA-A, Up-Regulation