title: Potency of GABA at human recombinant GABA(A) receptors expressed in Xenopus oocytes: a mini review.
abstract: GABAA receptors are members of the ligand-gated ion channel superfamily that mediate inhibitory neurotransmission in the central nervous system. They are thought to be composed of 2 alpha (α), 2 beta (β) subunits and one other such as a gamma (γ) or delta (δ) subunit. The potency of GABA is influenced by the subunit composition. However, there are no reported systematic studies that evaluate GABA potency on a comprehensive number of subunit combinations expressed in Xenopus oocytes, despite the wide use of this heterologous expression system in structure-function studies and drug discovery. Thus, the aim of this study was to conduct a systematic characterization of the potency of GABA at 43 human recombinant GABA(A) receptor combinations expressed in Xenopus oocytes using the two-electrode voltage clamp technique. The results show that the α-subunits and to a lesser extent, the β-subunits influence GABA potency. Of the binary and ternary combinations with and without the γ2L subunit, the α6/γ2L-containing receptors were the most sensitive to GABA, while the β2- or β3-subunit conferred higher sensitivity to GABA than receptors containing the β1-subunit with the exception of the α2β1γ2L and α6β1γ2L subtypes. Of the δ-subunit containing GABA(A) receptors, α4/δ-containing GABA(A) receptors displayed highest GABA sensitivity, with mid-nanomolar concentrations activating α4β1δ and α4β3δ receptors. At α4β2δ, GABA had low micromolar activity.
authors: Faculty of Pharmacy A15, University of Sydney, Sydney, NSW, 2006, Australia.
authors: Nasiara
authors: N
authors: Karim
authors: Petrine
authors: P
authors: Wellendorph
authors: Nathan
authors: N
authors: Absalom
authors: Graham A R
authors: GA
authors: Johnston
authors: Jane R
authors: JR
authors: Hanrahan
authors: Mary
authors: M
authors: Chebib
mesh_terms: D000818:Animals; D015870:Gene Expression; D006801:Humans; D009865:Oocytes / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism*; D014981:Xenopus / Q000235:genetics* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D021122:Protein Subunits; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid