Ranolazine inhibits sodium current in human breast cancer cells. Sodium currents (INa) from MDA-MB-231 breast cancer cells stably expressing null target shRNA (shCTL) were studied in voltage-clamp mode with the whole-cell configuration of the patch clamp technique. A, Left, representative INa-voltage traces obtained from one cell before (vehicle) and after 50 μM ranolazine treatment (Rano). Right, mean ± s.e.m. steady-state INa-voltage relationships obtained from cancer cells before and after incubation with 50 μM ranolazine (n = 12 cells) from a holding potential of −100 mV. There is as statistical difference between the two conditions for voltages ranging from −35 to +40 mV (p < 0.001, Wilcoxon test). B, Availability-voltage relationships obtained in presence (red trace) or not (vehicle, black trace) of 50 μM ranolazine. There is a significant leftward shift of the availability-voltage relationship in presence of ranolazine (p < 0.001). The half (1/2)-inactivation voltage was shifted from −84.1 ± 1.4 mV to −90.3 ± 1.7 mV in absence and presence of ranolazine, respectively. C, Activation-voltage relationships obtained in presence (red trace) or not (vehicle, black trace) of 50 μM ranolazine. There is a significant leftward shift of the activation-voltage relationship in presence of ranolazine, and the 1/2-activation voltage was shifted from −37.1 ± 1.0 mV to −39.2 ± 0.6 mV in absence and presence of ranolazine, respectively. (p < 0.01, Wilcoxon test).