Charge neutralizations in the domain 2 voltage sensor of NaV1.4 differentially influence gating modification by Tz1. (A) Representative current–voltage plots of the indicated NaV1.4 mutant channels in the absence (open circles) and presence (closed circles) of 5 µM Tz1 without (gray) or with (black) a prepulse. Continuous curves are data fits according to Eq. 1. (B; top) Estimates for the half-maximal activation voltages under control conditions (Vm) and for channels activated (Vm + ΔVa) and inhibited (Vm + ΔVi) by Tz1 according to data fits with Eq. 1. (Bottom) Probabilities of channels to be preactivated (gray bars; Pa) or inhibited (white bars; Pi) by Tz1 in absence (−) or presence (+) of a prepulse. Pa and Pi values were estimated from current–voltage plots as shown in A. Ptox, the probability of channels to be modified by Tz1, is displayed as the sum of Pa and Pi values, i.e., is denoted by the total height of the histogram bars. The number of independent experiments for control conditions and with Tz1, respectively, is indicated in parentheses.
