Figure 8.
Figure 8. Mexiletine blocks IKr channels. (A, top) IKr current traces recorded in father and proband iPSC-CMs during a 2-s depolarizing test pulse to 30 mV followed by a 2-s repolarizing pulse to −40 mV (holding potential was −40 mV) at 0.1 Hz in control conditions (black traces and arrows) and in the presence of 50 µM mexiletine (gray traces and arrows). 30 µM chromanol 293B was added to block IKs. (bottom) Mexiletine (50 µM)-sensitive potassium currents in iPSC-CMs subtracted from the top recordings. Dashed lines, zero current. (B) 50 µM mexiletine significantly blocked IKr tail current at −40 mV in iPSC-CMs from the father (WT = 897K/K, P < 0.05 vs. control) and proband (897K/T, P < 0.05 vs. control). Data are shown as means ± SEM.

Mexiletine blocks IKr channels. (A, top) IKr current traces recorded in father and proband iPSC-CMs during a 2-s depolarizing test pulse to 30 mV followed by a 2-s repolarizing pulse to −40 mV (holding potential was −40 mV) at 0.1 Hz in control conditions (black traces and arrows) and in the presence of 50 µM mexiletine (gray traces and arrows). 30 µM chromanol 293B was added to block IKs. (bottom) Mexiletine (50 µM)-sensitive potassium currents in iPSC-CMs subtracted from the top recordings. Dashed lines, zero current. (B) 50 µM mexiletine significantly blocked IKr tail current at −40 mV in iPSC-CMs from the father (WT = 897K/K, P < 0.05 vs. control) and proband (897K/T, P < 0.05 vs. control). Data are shown as means ± SEM.

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