Figure 1.
The newly identified BrS-associated Nav1.5 variant Y87C exerts dominant-negative effect over WT channels. (a) Representative whole-cell INa traces recorded from TsA-201 cells transiently transfected with 100% WT Nav1.5, 50% WT + 50% empty vector, 100% Y87C, or 50% WT + 50% Y87C. (b) Current density-voltage relationships of the four listed conditions. (c) Steady-state inactivation (SSI, left) and activation (right) relationships obtained using the Boltzmann equation. Whole-cell patch clamp protocols are given under the respective curves. (d) Peak current densities of each group under unsaturated conditions. Peak current density of WT + Y87C is significantly lower than that of WT + empty vector, indicating that Y87C exerts a dominant-negative effect over WT channels. Values pertaining to the biophysical properties are shown in Table 1. Data are presented as mean ± SEM. One-way ANOVA. *, p < 0.05. Other p values in (D): WT vs. WT + empty vector, p = 0.0002; WT vs. Y87 C, p < 0.0001; WT vs. WT + Y87 C, p < 0.0001.