Fig. 2.

Block of resting and inactivated rNav1.4 Na⁺ channels at various ranolazine concentrations. A, representative current traces are superimposed before and after application of 100 μM ranolazine. Cells were held at −140 mV and received 5-ms test pulses of +30 mV at 30-s intervals. B, representative current traces are superimposed for ranolazine concentrations of 0, 30, and 100 μM. After a −70-mV conditioning pulse for 10 s, Na⁺ currents were evoked by the 5-ms test pulse at 30 mV, administered every 30 s. An interpulse of 95 ms at the holding potential was inserted to allow the recovery of the drug-free inactivated Na⁺ channels. C, a dose-response curve was constructed using data described in Fig. 2A (resting block: ■, n = 5) and 2B (inactivated block: ▲, n = 6). The peak current was measured, normalized to the control (0 μM), and plotted against the ranolazine concentration. The curve was fitted with the Hill equation (solid line). The IC₅₀ value for resting block was >300 μM and could not be experimentally attained. The IC₅₀ value for inactivated block was estimated at 75.0 ± 3.5 μM (Hill coefficient, 1.41 ± 0.10, n = 6).