Figure 3.

Electrophysiological Properties of iPSC-CMs and AP Response to I_Kr Blockade

(A) Representative current traces of the I_Kr in Control-, LQT2^A422T-, and LQT2^A422T-corr-iPSC-CMs.

(B) Average current-voltage relationships for peak tail currents in Control-, LQT2^A422T-, and LQT2^A422T-corr-iPSC-CMs (independent experiments, n = 8, 6, and 5 from independent differentiation experiments, n = 4, 4, and 3, respectively; mean ± SEM; p = 0.029; two-way repeated measures ANOVA). ^∗p < 0.05, Fisher's LSD post hoc test for Control versus LQT2^A422T; †p < 0.05, LQT2^A422T-corr versus LQT2^A422T.

(C) Representative traces of AP with 1-Hz pacing.

(D) APD₅₀ and APD₉₀ in Control-, LQT2^A422T-, and LQT2^A422T-corr-iPSC-CMs (independent experiments, n = 6, 9, and 11, from independent differentiation experiments, n = 5, 6, and 5, respectively; mean ± SEM; p = 0.010 and p = 0.025 for APD₅₀ and APD₉₀, respectively; one-way ANOVA). ^∗p < 0.05, Fisher's LSD post hoc test for APD₅₀ and APD₉₀.

(E) Representative AP traces changed by I_Kr blockade.

(F) Percentage of APD prolongation after E4031 treatment (%ΔAPD) at 1-Hz pacing in each cell line. %ΔAPD₅₀ and %ΔAPD₉₀ in Control-iPSC-CMs and LQT2^A422T-corr-iPSC-CMs versus LQT2^A422T-iPSC-CMs (independent experiments, n = 7, 10, and 10 from independent differentiation experiments, n = 5, 5, and 6 in Control-, LQT2^A422T-, and LQT2^A422T-corr-iPSC-CMs, respectively; mean ± SEM; p = 0.001; two-way repeated measures ANOVA). ^∗p < 0.05, Fisher's LSD post hoc test.

See also Figure S2.

APA, action potential amplitude; MDP, maximum diastolic potential.