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, , 2020.

A. , Top panel: representative traces of ventricular APs measured in IRX5-A150P and -N166K mutated and control hiPS-CMs paced at 700ms cycle length with their corresponding first derivatives of the stimulus (S) and of the AP upstroke phases (arrows) of the APs

B. , Resting membrane potentials (RMPs) measured from ventricular APs paced at 700ms cycle length with or without in-silico IK1 injection. Mean and SEM are indicated; n: same as in A and C

C. , Top panel: representative traces of ventricular APs measured in A150P and N166K IRX5-mutated and control hiPS-CMs paced at 700ms cycle length with their corresponding first derivatives of AP upstroke (arrows)

, Representative traces of INa-TTX-sensitive and ICa,L-Nifedipine-sensitive in control hiPS-CMs, obtained by subtraction of the current recorded before and after application of the inhibitors, when applying typical ventricular-like AP voltages

E. , Superimposed representative traces of INa recorded when applying the depicted voltageclamp protocol, and mean current densities (pA/pF) vs. membrane potential (EM) recorded in hiPS-CMs. *** and ### p<0.001 vs. control (n=27) for respectively IRX5-A150P (n=31) and -N166K hiPS-CMs (n=30) (Two-way Anova with Bonferroni post hoc test)

F. , Superimposed representative traces of ICa,L recorded when applying the depicted voltageclamp protocol, and mean current densities (pA/pF) vs. membrane potential (EM) obtained in hiPS-CMs

, Figure 6: IRX5 interacts with SCN5A and GJA5 promoters

A. , Schematic representation of potential binding sites for IRX5 (BS, in green; numbers indicate position referring to TSS) on SCN5A promoter identified in-silico, and PCR amplification using primers specific for each BS after hiPS-CMs chromatin immunoprecipitation (ChIP) with an antibody against IRX5

, TSS: transcription starting site, DNA relative to intergenic region (IR)

. ***, 001 vs. control in IRX5-mutated samples, p.0

B. , IRX5 interaction with GJA5 promoter obtained as in A Ctrl: n=6; A150P: n=5; N166K: n=7, 2020.