Altered receptor subtypes in the forebrain of GABA_A receptor δ subunit-deficient mice: recruitment of γ2 subunits

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• 作者：Korpi ; E.R. ; Mihalek ; R.M. ; Sinkkonen ; S.T. ; Hauer ; B. ; Hevers ; W. ; Homanics ; G.E. ; Sieghart ; W. ; et. al.
• 关键词：knockout mouse line ; quantitative autoradiography ; western blotting ; subunit level ; immunoprecipitation ; subunit assembly ; DMCM ; methyl-6 ; 7-dimethoxy-4-ethyl-β ; -carboline ; Ro 15-4513 ; ethyl-8-azido-5 ; 6-dihydro-5-methyl-6-oxo-4H-imidazo[1 ; 5-a][1 ; 4]benz
• 刊名：Neuroscience
• 出版年：2002
• 出版时间：February 22, 2002
• 年：2002
• 卷：109
• 期：4
• 页码：733-743
• 全文大小：545 K

文摘

A GABA_A receptor δ subunit-deficient mouse line was created by homologous recombination in embryonic stem cells to investigate the role of the subunit in the brain GABA_A receptors. High-affinity [³H]muscimol binding to GABA sites as studied by ligand autoradiography was reduced in various brain regions of δ^−/− animals. [³H]Ro 15-4513 binding to benzodiazepine sites was increased in δ^−/− animals, partly due to an increment of diazepam-insensitive receptors, indicating an augmented forebrain assembly of γ2 subunits with α4 subunits. In the western blots of forebrain membranes of δ^−/− animals, the level of γ2 subunit was increased and that of α4 decreased, while the level of α1 subunits remained unchanged. In the δ^−/− forebrains, the remaining α4 subunits were associated more often with γ2 subunits, since there was an increase in the α4 subunit level immunoprecipitated by the γ2 subunit antibody. The pharmacological properties of t-butylbicyclophosphoro[³⁵S]thionate binding to the integral ion-channel sites were slightly altered in the forebrain and cerebellum, consistent with elevated levels of α4γ2 and α6γ2 subunit-containing receptors, respectively.