Fig 5.

E-4031 block of hERG1a/1b and 1a channels assessed with conventional step protocol at room temperature. Currents were recorded before drug application by stepping from -80 to +20 mV for 4 s and then to -50 mV for 5 s with 15 s interpulse interval. Channels were held closed at -80 mV for 10 min in the presence of E-4031 and then subjected to 20 voltage pulses in the continued presence of the drug. A, steady-state dose-response curves for hERG 1a and 1a/1b channels. The IC₅₀ values for E-4031 drug block for hERG 1a and hERG 1a/1b channels were 6.2 ± 1.1 nM and 25.6 ± 4.3 nM, respectively. B, peak tail current amplitudes plotted as a function of number of pulses and fit to an exponential function to measure the time course of block. Development of E-4031 block is slower for hERG1a/b channels.