Figure 1.

Ca_V1.3 Ca²⁺ channels manifest ultrastrong CDI driven exclusively by CaM. A, Prototypical CDI exhibited by Ca_V1.2 Ca²⁺ channels (α_1C/β_2a/α₂δ). Top, Voltage protocol and exemplar whole-cell currents. Here and throughout, the scale bar for current refers to Ca²⁺ waveforms, and the Ba²⁺ waveforms are scaled down approximately three times to facilitate visual comparison of decay kinetics. Top middle, Fraction of peak current remaining after 50 ms depolarization (r₅₀), plotted as a function of step potential. The distance between Ba²⁺ and Ca²⁺ relations gauges kinetics of CDI. Bottom middle, Fraction of peak current remaining after 300 ms depolarization (r₃₀₀), plotted as a function of step potential. The distance between Ba²⁺ and Ca²⁺ relations gauges steady-state extent of CDI. Bottom, Normalized I--V relation, taken from peak Ca²⁺ currents evoked by voltage steps to the indicated potentials. B, Ultrastrong CDI exhibited by Ca_V1.3 Ca²⁺ channels (α_1Dsh/β_2a/α₂δ). Format as above in A. Bottom middle, Distance between Ba²⁺ and Ca²⁺ r₃₀₀ relations at −10 mV (f₃₀₀) furnishes simple metric of steady-state extent of CDI. Bottom, Dashed curve reproduces fit to normalized I–V relation for Ca_V1.2 from A. f₅₀ = 0.70 ± 0.02 (n = 11); f₃₀₀ = 0.63 ± 0.02 (n = 11). C, Elimination of CDI during coexpression of Ca_V1.3 channels with CaM₁₂₃₄. Format as above in A. f₅₀ = 0.04 ± 0.03 (n = 7); f₃₀₀ = 0.06 ± 0.04 (n = 7). D, CDI during coexpression of Ca_V1.3 channels with CaM_WT. Format as above in A. No appreciable difference from profile in B. f₅₀ = 0.69 ± 0.04 (n = 5); f₃₀₀ = 0.72 ± 0.02 (n = 5).