Figure 4.

Action potential repolarization, persistent Na⁺ current (I_NaP) and intracellular Ca²⁺ handling in cardiomyocytes derived from induced pluripotent stem cells from the proband (BrS1) and his unaffected brother (Ctl1). (A) Representative action potentials recorded at a pacing cycle length of 700 ms in Ctl1 and BrS1 cardiomyocytes derived from induced pluripotent stem cells. (B) Box plot of action potential duration (APD) at 30% (APD30), 50% (APD50), and 90% (APD90) of full repolarization. Statistical test: two-way analysis of variance with Bonferroni test for multiple comparisons. (C) Representative currents recorded during 1-s voltage-clamp ramps from −120 mV to +40 mV (inset; stimulation frequency: 0.2 Hz) before (Control) and after tetrodotoxin (TTX) perfusion (top traces) in Ctl1 and BrS1 cardiomyocytes derived from induced pluripotent stem cells Bottom traces show the corresponding TTX-sensitive currents. (D) Box plot of the TTX-sensitive I_NaP at −20 mV. Mann–Whitney test. (E) Representative examples of early afterdepolarizations recorded in spontaneously beating cardiomyocytes differentiated from BrS101 and BrS103 iPSC clones (BrS1 patient). (F) Early afterdepolarization incidence in the different cardiomyocytes derived from induced pluripotent stem cell lines. χ² test; P values vs. Ctl1. (G) Representative [Ca²⁺]_i transients from Ctl1 and BrS1 cardiomyocytes derived from induced pluripotent stem cells with an example of abnormal Ca²⁺ oscillations following peak [Ca²⁺]_i transient in BrS cardiomyocytes derived from induced pluripotent stem cells. (H) Box plot of [Ca²⁺]_i transient 75% decay time (Ca²⁺ transient 75%) in Ctl1 and BrS1 cardiomyocytes derived from induced pluripotent stem cells Mann–Whitney test.