Figure 1.

ML252 inhibits Kv7.2 and Kv7.3 homomeric channels with rapid onset. (A to C) Exemplar records from Xenopus oocytes expressing indicated channel types, in (top) 0 µm or (bottom) 10 µm ML252. Oocytes were held at −80 mV and pulsed between −140 and +40 mV in 10 mV steps. (D and E) Oocytes expressing (D) Kv7.2 (n = 7) or (E) Kv7.3* (n = 9) were pulsed from −80 mV to +20 mV for 1 s at 0.1 Hz, and ML252 was applied after the first pulse. (F) Concentration response for ML252 measured at +20 mV from oocytes injected with Kv7.2 (n = 4–13; IC50 = 0.88 μm), Kv7.3 [A315T] (Kv7.3*; n = 8–13; IC50 = 2.71 μm), WT Kv7.3 (Kv7.3; n = 4–8; IC50 = 1.32 μm), Kv7.2/Kv7.3 (n = 3–11; IC50 = 4.05 μm), and Kv7.5 (n = 5–6; IC50 = 6.70 μm). (G) ML252 (black, 10 μm) or XE991 (green, 100 μm) were applied after the first pulse as shown. Oocytes expressing Kv7.2 were pulsed for 1 s at +20 mV, from a holding potential of −80 mV (0.1 Hz). (H) Maximal inhibition of Kv7.2/Kv7.3 heteromers in 100 μm ML252 (black) or XE991 (gray).