Figure 2.
CaV1.2 mutations selectively alter CDI versus VDI. (A) Exemplar whole-cell current traces (left) in Ba2+ demonstrate robust VDI (shaded blue) in WT CaV1.2 expressed with the β1b auxiliary subunit. Population data plotted for multiple voltages (right) demonstrates an increase in VDI with increasing voltage. Blue shading indicates the amount of VDI. r300 quantifies VDI as the ratio of current remaining after 300 ms and is displayed for the 30 mV step. Data are plotted ± SEM here and throughout. (B and C) VDI is significantly decreased by mutations L762F and E1496K. ****, P = 0.0005; **, P = 0.0042 determined via a one-way ANOVA with Dunnett’s multiple comparison test. (D–F) Mutations I1475M, I1166V, and I1166T, respectively, do not alter VDI. (G) Exemplar whole-cell current traces (left) in Ba2+ (black) and Ca2+ (red) demonstrate robust CDI (shaded peach) in WT CaV1.2 expressed with the β2a auxiliary subunit. Population data plotting the r300 value for multiple voltages (right) demonstrates minimal VDI (black) under these experimental conditions, and an expected U-shaped dependence of CDI on voltage (red). Peach shading indicates the amount of CDI, quantified by the difference between r300 values in Ca2+ versus Ba2+ (f300). The f300 value is given for the 30 mV data and is displayed ± SEM. Error bars indicate SEM here and throughout. (H and I) CDI is not significantly altered by mutations L762F or E1496K. (J–L) Mutations I1475M, I1166V, and I1166T, respectively, reduce CDI, with I1166T having the largest effect. *, P = 0.0451; ***, P = 0.0002; ****, P ≤ 0.0001 determined via a one-way ANOVA with Dunnett’s multiple comparison test.