RYR2 and Arrhythmia: PDE4D-KO CMs also showed increased arrhythmia susceptibility but a significantly lower number of extra beats as compared to PDE4B-KO cells (Figure 5E) suggesting that both PDE4B > PDE4D are critical regulators of arrhythmia susceptibility, and that PDE4B activity might also be, at least in part, associated with the RyR2 microdomain.