Comparison of the model P_OPEN to the Q_On-V relationship and steady-state ionic currents in a physiologically relevant cation gradient. In A, the Q_On-V relationship of R666G gating charge displacement is compared with the voltage dependence of the relative open probability of the R666G gating pore derived from the best fit parameters of the model in Fig. 6. The solid black line represents the least-squares fit of a single Boltzmann function to the experimental Q_On-V data, yielding the following parameters: V_1/2 = −48.4 ± 1.0 mV, k = 13.8 ± 0.3 mV, n = 9. In comparison, the gray line represents the single Boltzmann function describing the voltage dependence of relative open probability of the R666G gating pore permeation pathway. The best fit parameters from this function are as follows: V_1/2 = −50 mV, k = 11.3 mV. The inverse relationship between R666G gating pore accessibility (note the inverted scale to the right) and the voltage dependence of gating charge movement supports the notion that cation access to the permeation pathway is controlled by S4 translocation (presumably the DIIS4 voltage sensor). In B, the I-V relationship of normalized cation currents flowing through the R666G gating pore in oocytes exposed to bath and internal solutions approximating the normal mammalian physiological Na⁺/K⁺ gradient is shown (n = 5). The solid line represents the behavior of the R666G gating pore current under these conditions, as predicted by the model (using parameters listed in Table I).