Figure 6

Mutation A735V prolongs the time constant of recovery from inactivation for NaV1.5 sodium channels expressed in hiPSC-CM and HEK293T cells. (a) Two pulse protocol to investigate the recovery from inactivation and representative current responses of WT and mutant A735V NaV1.5 channels expressed in HEK293T cells or hiPSC-CMs. Inter-pulse interval (Δt) varied from 1 to 1000 ms (inter-pulse voltage: -120 mV). (b,c) Time dependent increase of relative current amplitudes (INa (pulse2)/INa (pulse1)) fitted by a bi-exponential function reveal two time constants (τ1 and τ2) for recovery from inactivation of WT and mutant A735V NaV1.5 channels expressed in HEK293T cells (b) and hiPSC-CMs (c; data points < 10 ms are not displayed for hiPSC-CMs, according to improper fast voltage clamp conditions with large cardiomyocytes). (d–f) Scatter plot and mean values (±s.e.m.) of fast (d) and slow time constants (e,f) of recovery from inactivation for WT and mutant A735V channels expressed in HEK293T cells (d,e) or hiPSC-CMs (f). - Data volume in (b,d) and (e): WT, n = 18; A735V, n = 16. Data volume in (c) and (f): WT, n = 6; A735V, n = 36.