Figure 5.

Two movements of the voltage sensor and pore. (Center) The normalized S4 Z movement and macroscopic current (2000 ion channels), calculated for a depolarizing potential to 60 mV from a holding potential of −80 mV, show that the S4 movement in the Z direction precedes ion conduction through the pore. The dashed line divides approximately the two time courses of major conformational changes between structure clusters shown in the right panel. (Top) The KDEs calculated based on the temporal occupancy of the structure clusters are shown at the top for three different times. Comparing the structure-cluster KDE at −80 mV holding potential (center panel (inset)) and 0.87 s after 60 mV depolarization, it can be seen that the initial movement of S4 in the Z-direction (∼9 Å) is fast. As time progresses (at 2 and 5.8 s), the S4 Z moves slower to a slightly higher Z position (∼1.4 Å, at 6 s) with high conductance. The pore opening from a small to a large pore diameter is also much slower than the initial S4 movement. (Right) The top panel identifies major cluster structures occupied at a holding potential of −80 mV (pink, green, and blue filled circles). They correspond to the KDE map at −80 mV (center panel), except the pink clusters do not show on the map scale. The colored arrows mark the most probable trajectories of the structures to the high SC clusters (black filled circle) during application of a depolarizing potential. The middle and bottom panels show the time progression of the probability of these trajectories (color coded) for two different membrane potentials, +60 mV (middle) and −40 mV (bottom).