Nonstationary noise analysis of Tz1 effects. (A) Mean current responses of NaV1.4 channels (bottom, I) and their ensemble variances (top, σ2) from at least 100 individual current traces elicited at the indicated voltages in the absence (black) and presence (gray) of 5 µM Tz1. (B) Variance as a function of mean current for several voltages in the absence (left) and presence (right) of Tz1. Continuous lines are results of global data fits according to Eq. 4. Data fits were constrained as described in Materials and methods. N is the estimate for the number of active channels in this particular experiment. (C) Estimated single-channel current (i) and maximal open probability (Po) as a function of voltage in the absence (open circles) and presence (closed circles) of Tz1 for the indicated channel types. Po values at −70 mV were set to zero for all channel variants in the absence of Tz1; for NaV1.4–G658N and NaV1.5, this was also done in the presence of Tz1 because channels are closed under these conditions. Data points, connected by straight lines, are presented as mean ± SEM. The numbers of individual experiments were n = 5, 5, 4, and 5.
