Figure 6. Model 2 for ClC-2 gating.

A, kinetic model built according to Scheme II that couples movement of the fast gate to Cl⁻ occupancy of the pore_. Rectangular boxes indicate four conformations: C = closed unprotonated, O = open unprotonated, C_H = closed protonated and O_H = open protonated. S_cen and S_ext anion binding sites are represented by dashed green and red circles, respectively. Cl⁻ is represented by a green sphere, H⁺ by a blue sphere and the fast gate by a red sphere. Protonation of the fast gate by is indicated by a blue sphere attach to a red sphere. Transitions between Cl⁻-free and Cl⁻-bound states are dictated by V_m-dependent rate constants. Transitions between unprotonated and protonated states are characterized by V_m-independent equilibrium constants and K_O, respectively. Fast gate is open by electrostatic repulsion when either a Cl⁻ (f₁ = 151) or H⁺ ion is bound (f_H = 8.46). B, simulated ionic currents from +60 mV to −180 mV, in 40 mV increments according to the voltage protocol shown on top. I_Cl(t) were simulated for [Cl⁻]_i = [Cl⁻]_o = 140 mm, pH_o = pH_i = 7.3. C, simulated time course of G_norm at −110 and +60 with [H⁺]_o from = 10⁻¹⁰ m to = 10^−6.4 m. D, opening time constant vs.[H⁺]_o. E, closing time constant vs.[H⁺]_o. Simulations were done using the parameter set listed in Table 1.