Fig. 6.
Inhibition by ABP-700 and CPM-acid of electrophysiologic currents evoked by 1 mM γ-aminobutyric acid (GABA) and mediated by α1β3γ2L γ-aminobutyric acid type A (GABAA) receptors. (A and B) Representative electrophysiologic traces recorded upon perfusing oocytes expressing α1β3γ2L GABAA receptors with 1 mM GABA alone for 70 s. Ten seconds into this activation period, (A) ABP-700 or (B) CPM-acid was added for 30 s. The gray bars highlight the periods when ABP-700 or CPM-acid was applied. For each compound, all traces were obtained from the same oocyte. As an example of how this inhibition was quantified, the trace exemplifying the inhibitory action of 2000 μM ABP-700 has several overlays. The dotted red line shows the interpolated line used as the baseline against which the effect of ABP-700 was quantified, the solid red line shows the point of maximum inhibition at the end of ABP-700 application, and the intervening red arrow quantifies the inhibitory effect of 2000 μM ABP-700 on the GABA-activated current. (C) ABP-700 and CPM-acid concentration response curves for inhibition of currents evoked by 1 mM GABA. Each symbol is the mean ± SD derived from five different oocytes. The curves are nonlinear least square fits of the two datasets to equation 2 (see Data Analysis section) with the maximum and minimum values constrained to 100% and 0%, respectively. For ABP-700 and CPM-acid, the respective half-maximal inhibitory concentrations for inhibition were 770 μM (95% CI, 590 to 1010 μM) and 1,450 μM (95% CI, 1,340 to 1,560 μM) with respective slopes of −1.3 (95% CI, −1.7 to −0.8) and –2.0 (95% CI, −2.4 to −1.6).