An allosteric kinetic scheme for slow inactivation of Shaker IR. (A) The kinetic scheme devised for U-type inactivation (Klemic et al., 2001) was modified to include blockade by internal TEA. The scheme contains three parallel activation pathways: C-inactivated, normal, and U-inactivated. Internal TEA binds with k_on = 2,400 mM⁻¹s⁻¹ and k_off = 2,400 s⁻¹. We changed the names of some variables such that: k_I = kp, k_-I = k-p, k_U = ki, and k_-U = k-i. All rate constants and allosteric factors are as in Klemic et al. (2001). (B) Simulated time course of macroscopic inactivation in response to a voltage step to 0 mV in the absence (thin trace) and presence of 0.6 mM TEA (thick trace). This TEA concentration is shown because we could not see crossing over of the traces for other TEA concentrations. (C) Normalized voltage dependence of the near equilibrium inactivation in the absence (thin trace) and presence of 5 mM internal TEA (thick trace). TEA produces a shift of −2 mV when fitted to a Boltzman distribution. (D) Normalized recovery from inactivation in the absence and presence of 5 mM TEA. The fast recovery time constant remained ∼15 ms under both experimental conditions, whereas the slow recovery retained a time constant of ∼840 ms. At 0-mV pulses, inactivation time constant changed from 7.7 s in the absence of TEA to 12.9 s with 5 mM TEA. The macroscopic inactivation rate decreased linearly with the fraction of unblocked current (see Fig. 7 D) with a slope of 0.065 s⁻¹ and constant of 0.065 s⁻¹. On the other hand, the macroscopic deactivation rate constant at −110 mV decreased with a slope of 1.5 ms⁻¹ as a function of the unblocked current, consistent with the magnitude and voltage dependence of k_-O.