Figure 4.

Voltage-gated sodium currents recorded from HEK293 cells expressing wild-type human Na_v1.2 only (WT), coexpressed wild-type and mutant (WT+R102X, WT+R102X-FlagN, WT+R102X-FlagC), and mutant only (R102X). A, Sodium currents of the WT channel and R102X mutant protein. Currents were evoked by a step depolarization to 0 mV from a holding potential of –120 mV. B, Peak sodium conductance–voltage relationships for WT (open triangle), WT+R102X (filled circle), WT+R102X-FlagN (open circle), and WT+R102X-FlagC (open square). The data points represent the average of g_Na. The lines represent the least squares fit of the data to a Boltzmann function, according to the equation g_Na/_maxg_Na = 1/{1+exp[Vg_0.5–V_g]/kg}, where_maxg_Na is the maximum value for the Na⁺ conductance, g_Na; Vg_0.5 is the half-activation potential at which g_Na is 0.5_maxg_Na; and kg is the slope factor. C, Steady-state voltage dependence of inactivation for each cell. Cells were prepulsed for 2 sec at various holding potentials (from –120 to 20 mV in 10 mV increments), and then Na⁺ current was evoked by a step depolarization to –10 mV. I_max is the peak amplitude of the Na⁺ current measured at a holding potential of –120 mV. The data points represent the average of I/I_max. The solid lines represent the least squares fit of the data to a Boltzmann function, according to the equation I/I_max = 1/{1 + exp[(V_h–V_½)/k]}, where I_max is the magnitude of the peak Na⁺ current observed at a holding potential of –120 mV; V_h is the holding potential; V_½ is the potential at which the Na⁺ current is half-maximal, and k is the slope factor. D, V_½ values for each cell with a long prepulse (2 sec) shown in C (n = 12 or 13). Each point is given as mean ± SEM. *Statistical difference at 1% level. E, Steady-state voltage dependence of inactivation for each cell. Cells were pre pulsed for 200 msec at various holding potentials (from –120 to 20 mV in 10 mV increments), and then Na⁺ current was evoked by a step depolarization to –10 mV. Solid lines were fitted by the equation shown in C. F, Recovery from inactivated state. Recovery ratios from the inactivated state (I/I_max) were measured for various interpulse intervals. The curves were fitted using a Boltzmann function as described above. Each point is given as mean ± SEM.