Fig. 4. Signal propagation from SAN to surrounding atria is altered in a Ca²⁺ channel variant.

A tissue of size 3 × 3 cm was modeled using a diffusion constant of 1.2 cm²/s in the direction of the monitored fiber and 0.25 cm²/s in the direction orthogonal to this. A spatial resolution of 151 × 151 nodes (0.02 cm) and temporal resolution of ∆t = 0.125 ms was used. The panels show the membrane potential as a function of time at six different locations of the modeled tissue for different scalings of a CACNA1C variant (the first variant of Supplementary Table S2). The center (blue) expresses membrane potential dynamics similar to that seen in single-cell experiments (Figs. 1 and 2), while near the borders (magenta and yellow), the action potentials are sharper and more alike to those presented in ref.⁶². The left panels (A) show the results in a model tissue with a smaller (radius 0.27 cm) SAN, and the right panels (B) show the results using a larger (radius 0.40 cm) SAN. In the variants with smallest effect ($ϵ\mathbf{=}-\frac{1}{4}$ and $ϵ\mathbf{=}\frac{1}{4}$), only the pacemaking frequency is altered, but in other variants, more radical phenotypes are observed. The $ϵ\mathbf{=}-\frac{1}{2}$ variant ceases pacemaking in the tissue with smaller SAN, and in the simulations with the larger SAN, all action potentials initiated by the $ϵ\mathbf{=}\frac{1}{2}$ variant SANCs are not successfully transmitted to the atrial tissue