Discovery and Characterization of a Potent and Selective Inhibitor of Aedes aegypti Inward Rectifier Potassium Channels
Figure 3
VU625 is a potent and preferential inhibitor of AeKir1 over AeKir2B in whole-cell electrophysiology.
(A) Normalized AeKir1 current-voltage relationships obtained from heterologous expression in T-Rex-HEK293 cells, illustrating VU625-dependent inhibition before (control) and after addition of 0.9 µM VU625. Residual AeKir1 currents were inhibited with 2 mM barium. Cells were voltage clamped at −75 mV and ramped between −120 mV and +60 mV. (B) Concentration-response curve of VU625 derived from patch clamp experiments (n = 4–6). The IC50 of VU625 is 96.8 nM (95% CI: 75.4–124.2 nM). (C) Concentration-response curves of current inhibition mediated by heterologous expression in Xenopus oocytes of AeKir1 (filled circles) and AeKir2B (open circles) channels after bath application of VU625. n = 4–5 oocytes per concentration. The calculated IC50 values of VU625 for AeKir1 and AeKir2B current inhibition are 3.8 µM (95% CI: 2.3–6.3 µM) and 45.1 µM (95% CI: 31.7–64.2 µM), respectively.