Figure 6: Individual conductance levels are correlated with the movement of specific voltage-sensing domains.
(a) Average single channel open probability for Nav1.4 during activation at 0 mV (black) overlaid with the probability for Nav1.4-WCW to be either fully open (PO, blue dots) or in a state associated with the S2 subconductance (PS2, magenta dots). PS2 is shown inverted and scaled to illustrate its similar time course to that of Nav1.4 macroscopic inactivation. (b) PO and PS2 are shown as in a overlaid with fluorescence signals from fluorophores attached to individual voltage sensors from domains I–IV in Nav1.4 (Supplementary Fig. S6). Because fluorescence signals were prohibitively difficult to reliably obtain below room temperature, these signals were uniformly scaled in time to account for the different temperatures at which the single channel (10 °C) and fluorescence (room temperature) were obtained (see methods). (c) Summary of the voltage dependence of the time constants for entry into the S2 and O conductance levels (see Fig. 5), and the fast time constant from exponential fits to the fluorescence responses from individual voltage-sensing domains (Supplementary Fig. S6), after scaling the fluorescence in time as described above.
