Experimental and simulated macroscopic sustained current. (a) Shown are experimental recordings of TTX-sensitive currents in response to depolarization (–10 mV, 100 milliseconds) from a –100 mV holding potential recorded in cells expressing WT (left) and Y1795C (right) channels. (b) Simulated WT (left) and Y1795C (right) currents generated using the Na⁺ channel Markov model shown in Figure 1. The reduced rate of open channel inactivation (UO → UIF) due to Y1795C is reflected in the longer time course of the macroscopic current decay (a and b, arrows). (c) Sustained current, normalized to peak current, is plotted as percent peak current for WT and Y1795C channels. The left panel is a summary of experimentally recorded I_sus (–10 mV, 100 milliseconds). The values are: WT, 0.07% ± 0.01 %, n = 7; Y1795C, 0.40% ± 0.04%, n = 10. The right panel shows the values simulated by the model using the gating parameters described in the text. In both the experimentally recorded and simulated currents, the sustained current (I_sus) relative to peak current (I_peak) is increased in Y1795C (I_sus/peak = 0.5%) compared with WT (I_sus/I_peak ≤ 0.1%).