Figure 5.

RyR2 Phosphorylation at s2808 and the Csq-2 Level Determine the Spark Distribution in Patients With and Without AF

(A) RyR2 distribution in a myocyte model was used to simulate the effects of Csq-2 and s2808 phosphorylation on spark activity. The resulting heat map at baseline is shown below and the spatial event distribution is shown on the right. (B) The effect of Csq-2 level and distribution (left) on RyR2 activity (right). The effective RyR open probability depends on the amount of free Csq-2, with a range that differs for atrial fibrillation (AF) (blue arrow) and NoAF (gray arrow). (C) Distribution of s2808 phosphorylated RyR2 in the model (left) and its effect on RyR2 activity (right). RyR2 open probability is assumed to depend on phosphorylation at s2808 in a sigmoidal fashion. Gray and blue areas correspond to the ranges for s2808 phosphorylation in NoAF and AF (from Figure 4B). (D to F) Spark heat maps (left) and spatial event distribution (right) are shown, taking into account Csq-2 levels and distribution (D), s2808 level and distribution (E), and the combined effects of Csq-2 and s2808 phosphorylation (F).