Figure 1: Timothy Syndrome mutations reduce CDI.

(a) Diagram of Timothy Syndrome mutations within human Ca_V1.2. Exon 8 is expected to be paired with exon 1a in cardiac channels. (b) Exemplar whole-cell current traces in Ca²⁺ (red) and Ba²⁺ (black). CDI is seen as the faster decay of the Ca²⁺ versus Ba²⁺ trace. Channels are co-expressed with β_2a to allow examination of CDI independent of VDI effects. In addition to their VDI effects, both Timothy Syndrome mutations confer a significant decrease in CDI (middle, right). Scale bars are 200 pA and refer to the Ca²⁺ trace. (c). Population data, the fraction of peak current remaining after 300-ms depolarization (r₃₀₀) is plotted for Ba²⁺ and Ca²⁺ currents. The difference between Ca²⁺ and Ba²⁺ relations at 30 mV (f₃₀₀) specifies the isolated effect of CDI. Error bars represent±s.e.m., n=10, 8 and 12 for WT, G402S and G406R, respectively.