Figure 4.
Baseline AP characteristics of control, LQT, HCM, and DCM hiPSC-CMs. (a) Typical recordings of ventricular-, atrial-, and nodal-like action potentials from hESC-CMs, control hiPSC-CMs, LQT hiPSC-CMs, HCM hiPSC-CMs, and DCM hiPSC-CMs. (b) Schematic diagram of a patch-clamp trace, showing how results were analyzed to calculate action potential duration at 50, 70, and 90% repolarization (APD50, APD70, and APD90, respectively). (c) APD50, APD70, and APD90 for each of the three myocyte subtypes in control, LQT, HCM, and DCM patient groups (n=70, 3 lines per cohort). (d) Representative recordings of ventricular-like action potentials from control hiPSC-CMs, LQT hiPSC-CMs, HCM hiPSC-CMs, and DCM hiPSC-CMs (n=70, 3 lines per cohort). Arrowheads show putative early afterdepolarizations (EADs) or delayed afterdepolarizations (DADs). (e) Magnification of the underlined segment of the LQT AP tracing shows a representative EAD waveform at an expanded timescale. (f) Magnification of the underlined segment of the HCM AP tracing shows a representative DAD waveform at an expanded timescale. (g) Percentage of disease-specific cardiomyocytes displaying DADs and EADs, respectively (Control: n=128 cells, 3 control subject lines; LQT: n=90 cells, 3 patient lines; HCM: n=134 cells, 3 patient lines; DCM: n=70 cells, 3 lines). Dashed lines show 0 mV. *** indicates P<0.001.