Biophysical properties of Na⁺ channels in iPSC-CMs. (A) TTX (50 µM)-sensitive averaged Na⁺ current traces recorded from father (WT, n = 27, three clones; left) and proband (LQT-3, n = 41, clone OA6 9Cr8; right) iPSC-CMs at −10 mV (100-ms pulses at 0.2 Hz from a −90-mV holding potential). Dashed lines, zero current. (insets) I_Na normalized to peak current reveal the presence of I_Na late current (I_NaL; arrow) in LQT-3 but not in WT iPSC-CMs. (B) Percentage of I_NaL with respect to peak current measured in three clones from the father, two clones from the mother, and three clones from the proband. (All three LQT-3 clones are P < 0.01 vs. each WT clone). The number of cells tested is indicated above each bar. (C) Steady-state availability in LQT-3 (proband, n = 27, averaged from two clones) and WT iPSC-CMs (father, n = 23, averaged from three clones; mother, n = 3, one clone; both are P < 0.001 vs. LQT-3). For each individual, data obtained from each clone are detailed in Table 1. (D) Recovery from inactivation in LQT-3 (proband, n = 6, clone OA6 9Cr8) and WT iPSC-CMs (father, n = 4, clone HR-I-2R 2Cr). Half-time in WT iPSC-CMs is P < 0.01 versus LQT-3. (E) Activation curve in LQT-3 (proband, n = 3, clone OA6 9Cr8) and WT iPSC-CMs (mother, n = 3, clone HR-II-9). V_1/2 in WT iPSC-CMs is not significantly different from LQT-3. Data are shown as means ± SEM.