Figure 4. High Ca²⁺ requirements for CDI.

A, exemplar currents from Ca_V2.1 permeating either Ca²⁺ (red) or Ba²⁺ (black) during a 1 s depolarization to 30 mV. B, similar protocol for Ca_V2.1 E3A. In both cases, 40 Ca²⁺/40 Ba²⁺ (mm) were used to increase current density. C, population data for WT and E3A channels, plotting the ratio of currents at 800 ms to peak current for Ba²⁺ and Ca²⁺ (mean ± SEM). Both WT and E3A have n = 5 cells each, with comparison between E3A and WT done using unpaired Student's t test (P > 0.05). D, Li⁺ currents through Ca_V2.1 EFb E3A channels are stable at ∼0.7 μm (left). Uncaging Ca²⁺ to ∼14 μm elicits a small amount of CDI (right). E, compiling traces from n = 19 cells where Ca²⁺ was uncaged to various levels yields a Ca²⁺ dose–response curve for CDI (red continuous line), defined here as CDI = r_400,before – r_400,after (red arrow in D), where r₄₀₀ = I(t_uncaging)/I(t_{uncaging + 400ms}). E, data points shown are mean ± STD, where fit is a Hill function with n_Hill = 2, IC₅₀ = 22 μm. Fit for CDF's Ca²⁺ sensitivity is reproduced as red dashed line for comparison.