Fig. 1.

Electrophysiological properties of single iPSC-CMs. a Examples of spontaneous action potentials recorded in CNTR-CMs and K219T-CMs (scale bar, 1 sec). b Dot plot with maximal diastolic potential (MDP) data recorded from CNTR-CMs and K219T-CMs, relative to all iPSC-CMs (quiescent and spontaneously active cells: −61.3 ± 7.4 mV vs. −56.8 ± 9.6 mV—left panel) or to the spontaneously active cell population only (right panel), showing a significant depolarization of K219T-CMs vs. CNTR-CMs in the first condition. CNTR-CMs: n = 45; K219T-CMs: n = 46. c, d Patch clamp analysis of AP properties in spontaneously active iPSC-CMs. (CNTR: n = 33; K219T: n = 24). Dot plots for the main excitability features measured from spontaneous action potentials: maximal upstroke velocity (dV/dt_max), overshoot (OV), action potential amplitude (APA) and action potential duration at 90% repolarization (APD₉₀) are shown in c. Representative spontaneous action potentials (left; scale bar, 100 ms) and dV/dt (right; scale bar, 1 ms) in d (CNTR: dV/dt_max = 18.4 ± 9.7 Vs⁻¹, n = 33; overshoot = 22.6 ± 11.2 mV, n = 33; APA = 86.4 ± 15.2 mV, n = 33. K219T-CMs: dV/dt_max = 11.8 ± 9.2 V s⁻¹, n = 24; overshoot = 12.3 ± 11.6 mV, n = 24; APA = 74.2 ± 16.1 mV, n = 24). e, f Patch clamp analysis of AP properties in iPSC-CMs electrically adjusted to −82 mV (evoked APs-CNTR: n = 45; K219T: n = 46). Dot plots for the main excitability features measured from evoked action potentials: maximal upstroke velocity (dV/dt_max), overshoot (OV), action potential amplitude (APA) and action potential duration at 90% repolarization (APD₉₀) are shown in e. Representative evoked action potentials (left; scale bar, 100 ms) and dV/dt (right; scale bar, 2 ms) in f. Measurements highlighted with blue symbols in c and e were obtained from action potentials shown in d and f. All values are reported as mean ± SD. *p < 0.05; **p < 0.005 (unpaired t-test). Data are relative to CMs differentiated from 2 lines from each subjects (2 CNTR and 3 K219T-LMNA)