Figure 5.

Functional Analysis of iPSC-CMs Using MEA Following I_Na Blockade

(A) Representative traces of FP in LQT3^N406K- and LQT3^corr-iPSC-CMs (left). FPDc at baseline in LQT3^N406K-iPSC-CMs was significantly shortened by gene correction (right) (independent experiments, n = 36 and 29 from independent differentiation experiments, n = 8 and 8 in LQT3^N406K- and LQT3^corr-iPSC-CMs, respectively; mean ± SEM; p < 0.05; unpaired Student's t test). ^∗p < 0.05.

(B) Representative traces of the FP following administration of 400 nmol/L (red) TTX in Control-, LQT3^N406K-, LQT3^corr-, LQT1^A344Aspl-, and LQT2^A422T-iPSC-CMs (left). The response to treatment with 400 nmol/L TTX was significantly larger in LQT3^N406K-iPSC-CMs than in Control-, LQT3^corr-, LQT1^A344Aspl-, and LQT2^A422T-iPSC-CMs (right) (independent experiments, n = 9, 11, 17, 5, and 5 from independent differentiation experiments, n = 4, 5, 4, 3, and 3 in Control-, LQT3^N406K-, LQT3^corr-, LQT1^A344Aspl-, and LQT2^A422T-iPSC-CMs, respectively; mean ± SEM; p < 0.001; one-way ANOVA). ^∗p < 0.05; Fisher's LSD post hoc test.

(C) Averaged %ΔFPDc on 10 μmol/L mexiletine in Control-, LQT3^N406K-, and LQT3^corr-iPSC-CMs (independent experiments, n = 7, 11, and 12 from independent differentiation experiments, n = 3, 3, and 5, respectively; mean ± SEM; p < 0.001; one-way ANOVA). ^∗p < 0.05; Fisher's LSD post hoc test.

(D) Comparison of AUCs for baseline FPDc and %ΔFPDc upon specific current blockade for recognizing disease-specific iPSC-CMs. Specific current blockade enhanced the accuracy of recognizing disease-specific iPSC-CMs.

See also Table S1.