Spontaneous and evoked action potentials are altered in R92Q hiPSC-CMs and I_Ca densities are reduced. (A) Representative whole-cell spontaneous action potentials recorded from WT and R92Q hiPSC-CMs are illustrated; dotted black lines indicate 0 mV. (B) Firing frequencies, maximum diastolic potentials (MDP), maximum upstroke velocities (dV/dt_max) and APD₅₀ measured in individual WT (n = 58) and R92Q (n = 29) hiPSC-CMs are plotted; mean values are also indicated and are provided in Table S3. (C) Representative whole-cell action potential waveforms evoked from a hyperpolarized membrane potential, as described in Materials and methods, in WT and R92Q cells are shown; dotted black lines indicate 0 mV. (D) dV/dt_max and APD₅₀ values measured in individual WT (n = 58) and R92Q (n = 29) cells are plotted; mean values are also indicated and are provided in Table S3. (E) Representative voltage-gated Ca²⁺ current (I_Ca) waveforms, elicited by voltage steps to test potentials between −40 and +15 mV (in 5-mV increments) from a HP of −50 mV, in WT and R92Q hiPSC-CMs are shown. (F) Mean ± SEM peak I_Ca densities in R92Q (n = 12) and WT (n = 15) hiPSC-CMs are plotted as a function of the test potential. Values in R92Q mutant cells are significantly different from those in WT cells at the +, P < 0.05; ‡, P < 0.01; and *, P < 0.001 levels. P values were calculated using a two-tailed Student’s t test.