Calcium dysregulation underlies phenotypic diversity in LQT2: Insights from induced pluripotent stem cell-derived cardiomyocytes of a KCNH2 p.Y427H family trio

Figure 3 Action potentials and rapid delayed rectifier potassium current characteristics of family trio induced pluripotent stem cell-derived cardiomyocytes. A: Representative action potentials under 0.5-Hz pacing from father induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) (a1), proband iPSC-CMs (a2), and mother iPSC-CMs (a3). Panel shows resting membrane potential and action potential amplitude (a4), while panels present statistical analysis of APD₉₀ and APD₅₀ (a5 and a6). Data represent n = 15 from 3 independent differentiations; B: Representative total potassium currents from father iPSC-CMs (b1), proband iPSC-CMs (b2), and mother iPSC-CMs (b3). Panel shows the I_Kr current, obtained by subtracting the current before and after E4031 treatment (b4). Panel represents the difference in I_Kr tail current density (b5 and b6). Data represent n = 6 from 3 independent differentiations. iPSC-CMs: Induced pluripotent stem cell-derived cardiomyocytes; APA: Action potential amplitude; RMP: Resting membrane potential.