Figure 5

Frequency-dependence of use-dependent block of Na _v 1.7 currents by ranolazine. Trains of twenty 30 msec duration pulses to -10 mV from a holding potential of -120 mV were applied at five different frequencies and were performed both before and after exposure to 10 μM ranolazine. Example traces from a HEK 293 cell expressing WT channels are shown in panels A and B. The peak for each pulse is normalized to the peak of the first pulse, and the values are plotted in panel C. The use-dependent block, defined as the ratio of the peak from the 20^th pulse normalized to the peak of the first pulse, was determined for each cell and the averages are plotted with the basal responses shown in grey and the ranolazine responses shown in solid bars. In each panel the two datasets are shown to compare the response to ranolazine in cells expressing WT (panel D, n = 5), the IEM mutant L858H (panel E, n = 4), or the PEPD mutant V1298F (panel F, n = 7), channels.