| Abstract: | GABAA receptor (GABAR) isoforms in the central nervous system are composed of combinations of α(1–6), β(1–4), γ(1–4), δ(1) and (1) subunit subtypes arranged in a pentamer. Many regions of the brain express high levels of mRNA encoding several different subunits and even multiple subunit subtypes. The stoichiometry of GABAR isoforms is unclear, and the number and identity of individual subunit subtypes that are coassembled remain uncertain. To examine the role of β subunit subtypes in the functional properties of GABARS and to determine whether multiple β subtypes can be coassembled in functional GABARs, plasmids containing cDNAs encoding rat β1 and/or β3, α5 and γ2L subtypes were cotransfected into L929 fibroblasts. The properties of the expressed receptor populations were determined using whole-cell and single-channel recording techniques. The α5β1γ2L isoform was less sensitive to GABA than the α5β3γ2L isoform. α5β1γ2L isoform currents were also insensitive to the allosteric modulator loreclezole, while α5β3γ2L isoform currents were strongly potentiated by loreclezole. Fibroblasts transfected with plasmids containing cDNAs for both β1 and β3 subtypes along with α5 and γ2L subtypes produced a receptor population with an intermediate sensitivity to GABA which was insensitive to loreclezole. These results suggest that functional GABARs can be formed that contain two different β subunit subtypes with properties different from receptors that contain only a single β subtype and that the β subunit subtypes influence the response of GABARs to GABA and to the allosteric modulator loreclezole. |
