Consistent with the model prediction, combined KD of PLN and NCX in the presence of perturbagens (fibroblasts co-culture and isoproterenol infusion) significantly increased the occurrence of arrhythmia-like phenotypes in ACMs compared to that after single PLN KD, from 37.5% to 43.2% of cells with AI>20 (Fig. 6C). Here, PLN is linked to cardiac arrhythmia.