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Evidence that GABA A Receptor Subunit mRNA Expression During Development Is Regulated by GABA A Receptor Stimulation
Author(s) -
Poulter Michael O.,
Ohannesian Lillith,
Larmet Yves,
Feltz Paul
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.68020631.x
Subject(s) - gabaa receptor , allopregnanolone , protein subunit , gabaa rho receptor , messenger rna , in situ hybridization , biology , interleukin 10 receptor, alpha subunit , gamma aminobutyric acid receptor subunit alpha 1 , interleukin 5 receptor alpha subunit , receptor , stimulation , medicine , endocrinology , microbiology and biotechnology , g alpha subunit , neuroactive steroid , biochemistry , gene
The expression of six mRNA species (α2, α3, α5, β2, β3, and γ2) encoding for GABA A receptor subunits was followed in cultured early postnatal cortical neurons by in situ hybridization histochemistry. In untreated control cultures it was found that these subunit mRNA expression profiles closely follow those seen during development in vivo. α3, α5, and β3 subunit expression declined, α2 expression increased, whereas β2 and γ2 subunit mRNA expression remained relatively constant. To test the hypothesis that GABA A receptor stimulation regulates these expression profiles, we tested the effect of a GABA A receptor positive modulator, allopregnanolone, and a GABA A receptor noncompetitive antagonist, tert ‐butylbicyclophosphorothionate (TBPS). It was found that allopregnanolone augmented the rate at which the α3, α5, or β3 subunit mRNA expression declined and prevented the increase in α2 subunit mRNA expression. As well, allopregnanolone down‐regulated β2 subunit mRNA expression. TBPS, on the other hand, up‐regulated α3, α5, β2, and β3 subunit mRNA expression. It also down‐regulated the expression of α2 subunit mRNA. Both allopregnanolone and TBPS had no effect on γ2 subunit mRNA expression. These results imply that the developmental switchover of GABA receptor subunit mRNA expression is regulated by GABA A receptor activity.