Figure 6.

Rad p.R211H insertion in an extra-familial control line by genome editing: electrophysiological characterization. (A) Representative action potential recordings from control (Rad WT) and mutated (Rad WT) conditions. (B) Box plots of peak to peak duration and action potential upstroke velocity (dV/dt max) of Rad WT and Rad WT cardiomyocytes derived from induced pluripotent stem cells Mann–Whitney test. (C) Mean action potential duration (APD) at 30% (APD30), 50% (APD50), and 90% (APD90) of full repolarization at a pacing cycle length of 1 s. Two-way ANOVA with Bonferroni test for multiple comparisons. (D) Early afterdepolarization incidence in Rad WT and Rad R211H ins cardiomyocytes derived from induced pluripotent stem cells. (E) Representative [Ca²⁺]_i transients obtained in Rad WT and Rad R211H ins cardiomyocytes derived from induced pluripotent stem cells and their corresponding fluorescence map. (F) [Ca²⁺]_i transient 75% decay time (Ca²⁺ transient 75%) in Rad WT and Rad R211H ins cardiomyocytes derived from induced pluripotent stem cells Mann–Whitney test. (G) Superimposed representative I_Na traces recorded in Rad WT and Rad R211H ins cardiomyocytes derived from induced pluripotent stem cells (upper panel; voltage-clamp protocol in inset) and mean (±SEM) current density-membrane potential relationships (bottom). *P < 0.05, **P < 0.01, and ***P < 0.001 (two-way analysis of variance with Bonferroni post hoc test for multiple comparisons). (H) Top: representative currents recorded during 1-s voltage-clamp ramps from −120 mV to +40 mV (stimulation frequency: 0.2 Hz) before (Control) and after tetrodotoxin (TTX) perfusion (top traces) in Rad WT and Rad R211H ins cardiomyocytes derived from induced pluripotent stem cells and corresponding TTX-sensitive persistent sodium current (I_NaP, bottom traces). Bottom: box plots of I_NaP density. Mann–Whitney test.