Figure 3

Sodium channels exhibit electrophysiological modifications in patient-specific iPSC-CMs. (A) Representative sodium currents recorded in CTRL and DM1 iPSC-CMs. The dashed line represents zero current. (B) Normalized current/voltage relationships recorded in CTRL (n = 12), DM1-300 (n = 11), and DM1-1300 (n = 13) iPSC-CMs. Sodium current densities were measured by normalizing current amplitudes to membrane capacitance and were plotted against voltage. (C) Steady-state activation of sodium currents from CTRL and DM1 iPSC-CMs. Activation curves were generated using a standard Boltzmann distribution: G(V)/G_max = 1/(1 + exp(- (V-V_1/2)/k)). Inset shows graph of V_1/2. (D) Steady state inactivation of CTRL (n = 12) DM1-300 (n = 9) and DM1-1300 (n = 12). Inactivation currents were obtained using 10-ms test pulses to – 10 mV after a 500-ms pre-pulse to potentials ranging from – 140 to – 20 mV. The inactivation values were fitted to a standard Boltzmann equation: I(V)/I_max = 1/(1 + exp((V − V_1/2)/k)) + C. (E) Recovery from inactivation values recorded from CTRL (n = 9), DM1-300 (n = 9), and DM1-1300 (n = 9) iPSC-CMs. The cells were depolarized to – 30 mV for 40 ms from a holding potential of – 100 mV to inactivate the Na⁺ channels. Test pulses were then applied to – 30 mV for 20 ms to measure current amplitudes, with an interval ranging from 0.1 to 4000 ms. The resulting curves were fitted with a two-exponential equation: (A_fast(1 – exp(− t/τ_fast)) + Aslow(1 − exp(− t/τ_slow)) + C). (F) The time constants of fast inactivation decay were plotted as a function of voltage for the CTRL and DM1 iPSC-CMs. The time constants were obtained using a single exponential function: (A(exp(− t/τ) + C). Bars indicate SEM. *p < 0.05, ***p < 0.001 (CTRL vs DM1-1300) and ^###p < 0.05 (DM1-300 vs DM1-1300) by ANOVA and Tukey’s post hoc test.