Fig. 3.

Fig. 3.

CCh induces more pronounced effects in S81L^homo compared to WT and S81L^het RA-treated hiPSC-CMs. (A) Representative spontaneous APs at baseline (left) and upon 10 µmol l⁻¹ CCh (right) in WT, S81L^het and S81L^homo RA-treated hiPSC-CMs. The slanted arrows near the APs in the presence of CCh indicate the last AP before cessation of spontaneous activity. (B) Average frequencies before and during application of CCh. CCh drastically reduces the spontaneous AP frequency of S81L^homo hiPSC-CMs. WT, n=10; S81L^het, n=9; S81L^homo, n=14. **P<0.01 (two-way repeated measures ANOVA and post-hoc Bonferroni corrected pairwise comparison). (C) Proportion of WT, S81L^het and S81L^homo hiPSC-CMs that became quiescent upon application of CCh. WT, n=10; S81L^het, n=9; S81L^homo, n=14. **P<0.01 (chi-square test, followed by Bonferroni corrected pairwise comparisons). (D) Representative APs (1 Hz overdrive stimulation) before and after the application of CCh. (E) Average maximal diastolic potential (MDP) at baseline and upon CCh in WT, S81L^het and S81L^homo RA-treated hiPSC-CMs (1 Hz overdrive stimulation). WT, n=17; S81L^het, n=10; S81L^homo, n=13. Effect of CCh on MDP is significantly more pronounced in S81L^homo hiPSC-CMs (P<0.05 interaction effect CCh×genotype; two-way ANOVA).