Fig. 6.

Block of inactivation-deficient rNav1.4-WCW and rNav1.4-WCW/F1579K Na⁺ channels. A, representative current traces of inactivation-deficient rNav1.4-WCW Na⁺ channel block were superimposed at various ranolazine concentrations. Cells were held at −140 mV and received 50-ms test pulses of +30 mV at 30-s intervals. B, a dose-response curve was constructed from the data presented in Fig. 6A. Both peak (■) and late (□) currents were measured, normalized to the control (0 μM), and plotted against ranolazine concentration. The curve was fitted with the Hill equation (solid lines). The IC₅₀ value for the peak current block was estimated 225.4 ± 16.3 μM (Hill coefficient, 0.92 ± 0.05) (n = 5) and the IC₅₀ value for rNav1.4-WCW of the late current was 2.4 ± 0.2 μM (1.15 ± 0.09) (n = 5). C, representative current traces of rNav1.4-F1579K inactivation-deficient Na⁺ channel block were superimposed at various ranolazine concentrations. Currents were evoked using the pulse-protocol represented in A. Peak and late Na⁺ currents were measured, normalized, and plotted against concentration as shown in B (triangles). The estimated IC₅₀ value for rNav1.4-F1579K inactivation-deficient channel block of the late current was 40.8 ± 1.3 μM (Hill coefficient, 1.12 ± 0.04) (n = 5).