Figure 4.

I_Kr densities in mutated and corrected LQT2-hiPSC-derived CMs. (A) Representative current traces elicited upon 4 s depolarizing voltage steps to −30, −20, and −10 mV from a holding potential of −40 mV, before and after the application of 1 μM E-4031. Inset: voltage protocol. (B) Typical tail currents measured after the depolarizing step to −10 mV in corrected (black) and mutated (red) LQT2-hiPSC-CMs, showing a bi-exponential decay. (C) Average current–voltage (I–V) relationships for I_Kr, measured at the end of the test pulses, in mutated (red) and corrected (black) LQT2-hiPSC-derived CMs. Inset: voltage protocol. * indicates statistical significance (P=0.046, two-way rmANOVA; Holm–Sidak test post hoc analysis: −20 mV: P=0.015, −10 mV: P=0.007, 0 mV: P=0.018, 10 mV: P=0.011, 20 mV: P=0.013). (D) Average I–V relationships for peak tail currents in mutated (red) and corrected (black) LQT2-hiPSC-derived CMs. * indicates statistical significance (P=0.039, two-way rmANOVA; Holm–Sidak test post-hoc analysis: −20 mV: P=0.008, −10 mV: P=0.004, 0 mV: P=0.005, 10 mV: P=0.004, 20 mV: P=0.006). Inset: voltage protocol.