Figure 3.

Altered analogue structure changes Golgi-selective accumulation. A. Various structural analogues described in the text. Calculated logP values for the compounds are: KK-123, KK-152, KK-139, and MQ-127: logP = 4.45, KK-148 and KK-150: logP = 6.12. B, C. Oocytes expressed GABA_A subunits α1β2γ2L. Responses to GABA showed potentiation in response to co-application of 0.5 μM KK-123 (B) but not in response to co-application of 0.5 μM KK-150. Oocytes were clamped at −70 mV. D, E. In neurons, co-localization of KK-123 or KK-150 click cyto-fluorescence (green) and giantin immunolabeling (red) is revealed by a line scan plot of red and green fluorescence intensity. The lines from which the data are derived are shown in the insets. F. Summary of potentiation of GABA responses in oocytes at varied compound concentrations. All compounds showed relative inactivity compared with KK-123. MQ-139 exhibited weak but detectable activity at 10 μM (n = 4 oocytes for each compound). Response to GABA alone is denoted by the dotted horizontal reference line. G. Summary of co-localization with giantin, reported by Pearsons’ r values for compound vs. giantin fluorescence, for all six analogues in neurons (n = 15 cells per condition from 3–4 independent experiments; asterisks indicate p < 0.05 after Bonferonni correction for multiple comparisons).