Fig. 4. Effect of ivabradine on heterologously expressed human Na_v1.5 channels. (a) Voltage-clamp protocol to obtain current voltage relationships. (b) Typical inward currents through recombinant Na_v1.5 channels expressed in tsA-201 cells as elicited by the voltage-clamp protocol shown in (a) for selected voltage steps (-60,-50,-40,-35,-30,-25, -20,-15, -10, and 0 mV). (c) Voltage clamp protocol to elicit maximal sodium current amplitude. (d) Typical sodium current for the voltage-clamp protocol shown in (c) under control conditions and in the presence of 1, 10, and 100 µM of ivabradine. (e) Maximal Na_v1.5 current amplitude as elicited repetitively at 1 Hz by a voltage-step to -10 mV as shown in (c, d) under control conditions and in the presence of ivabradine. (f) Summary of normalized steady-state Na_v1.5 current amplitudes for all ivabradine concentrations tested. The line represents a non-linear fit with a Hill equation.