Figure 5.
The α6(R100Q) polymorphism causes an increase in flunitrazepam sensitivity when coexpressed with either γ2 or δ subunits. A, Representative current traces from oocytes demonstrate the effect of flunitrazepam on δ and γ2 subunit-containing GABARs. B, Data and sigmoid fits show percentage of maximal current versus [GABA] for GABARs of the indicated subunit compositions with and without of 1 μm flunitrazepam [α6β3γ2, n = 4 in control, n = 3 in Flu; α6(R100Q)β3γ2, n = 3 in control, n = 4 in Flu; α6β3δ, n = 9 in control, n = 7 in Flu; and α6(R100Q)β3δ, n = 6 in control, n = 5 in Flu]. C, Plots show peak enhancement of GABA current by 1 mm flunitrazepam calculated from the data in B and corresponding Gaussian fits for γ2 and δ subunit-containing GABARs (n=4 for each subunit combination tested). D, Flunitrazepam dose–response curves of recombinant GABARs in the presence of GABA concentrations at which maximum benzodiazepine potentiation was observed in the γ2 and δ subunit-containing receptors in B [i.e., 10 μm GABA for α6β3γ2 and α6(R100Q)β3γ2; 100 nm GABA for α6β3δ and α6(R100Q)β3δ; n=3 each]. Box in C indicates the flunitrazepam concentration (1 μm) used in A and B. In B–D, data are normalized to the saturating GABA response in each oocyte in control, averaged across oocytes and presented as percentage ± SD.