Figure 2.

Functional Analysis of iPSC-CMs Using MEA Following I_Kr Blockade

(A) Representative traces of FP in Control-, LQT2^A422T-, LQT2^A422T-corr-, and LQT2^G601S-iPSC-CMs.

(B) FPDc baseline data in Control-, LQT2^A422T-, LQT2^corr-, and LQT2^G601S-iPSC-CMs (independent experiments, n = 45, 35, 12, and 9 from independent differentiation experiments, n = 16, 11, 6, and 3, respectively; mean ± SEM; p = 0.001; one-way ANOVA). ^∗p < 0.05, Fisher's LSD post hoc test.

(C) Representative traces of the FPD following administration of 30 nmol/L (red), 100 nmol/L (green), and 300 nmol/L (blue) E4031.

(D) Averaged FPDc ratio before and after E4031 treatment (%ΔFPDc) in Control-, LQT2^A422T-, LQT2^A422T-corr-, LQT2^G601S-, and LQT1^A344Aspl-iPSC-CMs. FPDc prolongation upon treatment with 100 and 300 nmol/L E4031 was smaller in LQT2^A422T- and LQT2^G601S-iPSC-CMs than in Control-, LQT2^corr-, or LQT1^A344Aspl-iPSC-CMs (independent experiments, n = 23, 24, 12, 9, and 12 from independent differentiation experiments, n = 8, 8, 6, 3, and 3 in Control-, LQT2^A422T-, LQT2^A422T-corr-, LQT2^G601S-, and LQT1^A344Aspl-iPSC-CMs, respectively; mean ± SEM; p = 0.025; two-way repeated measures ANOVA). ^∗p < 0.05, Fisher's LSD post hoc test.

(E) Examples of EADs. EAD documented in a sample of LQT2^A422T-iPSC-CMs before E4031 treatment (upper) and following 30 nmol/L E4031 treatment (lower).

(F) Percentage of samples in which EADs occurred in Control-, LQT2^A422T-, LQT2^A422T-corr-, and LQT2^G601S-iPSC-CMs. The number on top of each bar shows the number of arrhythmic events. ∗p < 0.05; Pearson's Chi-square test.

See also Figure S1.