Figure 6. A sodium channel gating model... | Rockefeller University Press

Figure 6.

$Figure 6. A sodium channel gating model for the distinct role of DIV in fast inactivation. (A) Kinetic model for sodium channel gating. The horizontal transitions from left to right reflect activation of the DI–III voltage sensors followed by pore opening, and the vertical transitions from bottom to top reflect activation of the DIV voltage sensor followed by occlusion of the pore by the fast inactivation motif. Rate constants and associated charges are listed in Table 1. The effects of the DIV-CN mutant were explained solely by reducing the charge and varying the rates associated with movement of the DIV voltage sensor only such that DIV was biased toward its activated conformation (red arrow; see Table 1 for parameter values). The effects of the DI/II/III-CN mutants were qualitatively explained by reducing the charge and varying the rates for only the middle set of transitions associated with movement of the DI–III voltage sensors (blue arrow; see Table 1 for parameter values). (B) Simulated current responses to families of depolarizing voltage steps as described for Fig. 1 B. (C) Simulated current responses to a steady-state inactivation protocol as described for Fig. 2 A. (D) Simulated peak conductance (closed circles) and steady-state inactivation (open circles) as a function of voltage for wild-type (black), DIV-CN (red), and DI/II/III-CN (blue) channels. (E and F) Simulated time courses for development (−60 to 0 mV) and recovery (−180 to −110 mV) from inactivation for wild-type (black) and DIV-CN (red) channels. Note that fraction inactivated/recovered was not computed as the direct probability of being in one of the model’s inactivated states but rather was obtained from simulated current responses as described in Figs. 3 B and 4 B. Simulations for DI/II/III-CN channels were similar to wild type.$

A sodium channel gating model for the distinct role of DIV in fast inactivation. (A) Kinetic model for sodium channel gating. The horizontal transitions from left to right reflect activation of the DI–III voltage sensors followed by pore opening, and the vertical transitions from bottom to top reflect activation of the DIV voltage sensor followed by occlusion of the pore by the fast inactivation motif. Rate constants and associated charges are listed in Table 1. The effects of the DIV-CN mutant were explained solely by reducing the charge and varying the rates associated with movement of the DIV voltage sensor only such that DIV was biased toward its activated conformation (red arrow; see Table 1 for parameter values). The effects of the DI/II/III-CN mutants were qualitatively explained by reducing the charge and varying the rates for only the middle set of transitions associated with movement of the DI–III voltage sensors (blue arrow; see Table 1 for parameter values). (B) Simulated current responses to families of depolarizing voltage steps as described for Fig. 1 B. (C) Simulated current responses to a steady-state inactivation protocol as described for Fig. 2 A. (D) Simulated peak conductance (closed circles) and steady-state inactivation (open circles) as a function of voltage for wild-type (black), DIV-CN (red), and DI/II/III-CN (blue) channels. (E and F) Simulated time courses for development (−60 to 0 mV) and recovery (−180 to −110 mV) from inactivation for wild-type (black) and DIV-CN (red) channels. Note that fraction inactivated/recovered was not computed as the direct probability of being in one of the model’s inactivated states but rather was obtained from simulated current responses as described in Figs. 3 B and 4 B. Simulations for DI/II/III-CN channels were similar to wild type.