Effect of voltage-sensor mutants on Tz1-induced gating modification. (A) Activation (open symbols) and deactivation (closed symbols) time constants of the indicated NaV1.4 mutant channels in the presence of 25 µM Tz1 were calculated from experiments as shown in Fig. 8 and plotted as a function of voltage (n = 3–8). The continuous lines are data fits according to Eq. 6. The gray line represents data of wild-type NaV1.4. (B) The gating charge involved in voltage-dependent activation (qa; white bars) and deactivation (qd; gray bars) in the presence of Tz1 is shown as histogram bars. τmax is the maximal time constant of the transition between the activated and the resting state of the channels, and V0 is the corresponding equilibrium voltage. Data were calculated from experiments as shown in A. The fractions of channels preactivated in the presence of Tz1 (Pa/Ptox) without (gray symbols; −pp) or with (black symbols; +pp) a prepulse were calculated from current–voltage plots to predict functional consequences of Tz1 interaction with wild-type and mutant NaV1.4 channels.
