Veratridine-activated Na currents cause Na concentration changes that are consistent with unrestricted cytoplasmic Na diffusion. (A) Conductance and membrane current records during application of 15 µM veratridine. As apparent in the records, veratridine activates no conductance in the absence of Na and K. Application of 120 mM Na in replacement for NMDG then activates an inward current that is initially 860 pA in magnitude and that decays by 13% over 90 s. Removal of veratridine reversibly reduces the Na-dependent current and conductance by 55%. Thus, 45% of the Na current may be carried by mechanisms other than veratridine-modified Na channels, and Fig. S3 gives evidence for nonselective cation channels in murine myocytes. (B) Na-defined current–voltage relations obtained by subtracting the records 3, 4, and 5 from record 2. During the 90 s of Na application (3′ to 5′), the Na-defined current–voltage relation shifts from having no clear reversal to having a reversal at +41 mV, indicating a subsarcolemmal Na concentration of 19.8 mM. (C) Veratridine-defined current–voltage relation. The current–voltage relations defined by removing (5–6) and reapplying (7–6) veratridine reverse at +62 mV, corresponding to a subsarcolemmal Na concentration of 11 mM.