Impact of stimulation frequency on I_NaL and I_Kr in the absence and presence of drugs. (A) Averaged sodium current traces recorded at −10 mV (100-ms pulses applied from a −90-mV holding potential) in LQT-3 iPSC-CMs in control conditions (left; n = 5) and in the presence of 50 µM mexiletine (right; n = 5) at 0.2 Hz (gray traces and arrows) and at 1.6 Hz (black traces and arrows) at low and high (insets) gain. Dashed lines, zero current. (B) Percent block of I_Na peak current (I_{Na peak}) and I_Na late current (I_NaL) at 0.2 and 1.6 Hz by 50 µM mexiletine alone (n = 6) and 50 µM mexiletine plus 5 µM flecainide (n = 3). One-way ANOVA followed by Tukey’s test: *, P < 0.01 versus paired I_{Na peak}; ^#, P < 0.01 versus I_{Na peak} at 0.2 Hz in the presence of mexiletine; ^δ, P < 0.01 versus I_NaL at 0.2 Hz in the presence of mexiletine. (C) Block of I_Kr channels by 50 µM mexiletine (Mex) and 5 µM flecainide (Flec) at 1.6 Hz in WT iPSC-CMs depolarized to 30 mV for 200 ms, from a holding potential of −40 mV, and repolarized at −40 mV for 200 ms. (D) Change in I_Kr tail current density measured at −40 mV after 200-ms test pulses at 30 mV in control condition (at 0.2 and 1.6 Hz), in the presence of 50 µM mexiletine and after the addition of 5 µM flecainide. *, P < 0.05 versus paired control; ^#, P < 0.05 versus mexiletine at 1.6 Hz. Data are shown as means ± SEM.