FIGURE 11.
Subunit stoichiometry and arrangement of α1β2γ2 GABAA receptors depends on the relative expression level of γ2 subunits. A summary of the flow cytometry and electrophysiology data supporting the existence of alternative α1β2γ2 receptor isoforms is shown. In the absence of the γ2 subunit (“No γ”, α:β:γ cDNA transfection ratio 1:1:0), α1β2 receptors represent a mixed population of 2α:3β receptors with β-α-β-β-α arrangement and 3α:2β receptors with β-α-β-α-α arrangement, the latter likely not functional (depicted as × through the pore of this receptor). With low levels of γ2 subunit expression (“Low γ”, α:β:γ cDNA transfection ratio 1:1:≤1), incorporation of the γ2 subunit into the pentamer preferentially occurs at the expense of β2 subunits, resulting in formation of 2α:2β:1γ receptors with β-α-γ-β-α arrangement and 3α:1β:1γ receptors with a β-α-γ-α-α arrangement. At higher levels of γ2 subunit expression (“High γ”, α:β:γ cDNA transfection ratio 1:1:≥1), γ2 subunits continue to replace β2 subunits but can also begin to replace α1 subunits, resulting mainly in formation of 2α:1β:2γ receptors with β-α-γ-α-γ arrangement. Of note, the results suggest that 1α:2β:2γ receptors with β-α-γ/δ-β-γ arrangement may also form (data not shown), but these are thought to represent a relatively minor population.