The modeling platform of this study is our recently developed human atrial myocyte model that enables the simulation of emergent spatiotemporal characteristics of intracellular Ca2+ dynamics [13] (link). Methods for simulation of tissue-level electrophysiology and its analysis are presented in the Supporting Information and are detailed in [35] (link). Contrary to most previous in silico studies of cAF, we performed a broad literature search on cellular remodeling to define the average remodeled parameter values (Figure 1A ) instead of using a single in vitro data set or small subset. We have included those remodeling targets that have been established in more than one study. Full sets of referenced human data are shown in Supporting Information (Tables S2 –S4 ).
The modifications of existing model components, as well as the simulation protocols are described in detail in the Supporting Information. Briefly, we reformulated the ICaL to increase the contribution Ca2+-dependent vs. voltage-dependent inactivation of the current, and decreased the time constants based on recent in vitro data [36] (link), Supporting InformationFigure S1 . Parameters of the SERCA pump have been modified according to a previously developed scheme [37] (link), [38] (link) to enable the representation of changed expression of phospholamban (PLB) and sarcolipin (SLN) in cAF.
In our analysis of cAF-related cellular remodeling, we use the following three biomarkers:
The modifications of existing model components, as well as the simulation protocols are described in detail in the Supporting Information. Briefly, we reformulated the ICaL to increase the contribution Ca2+-dependent vs. voltage-dependent inactivation of the current, and decreased the time constants based on recent in vitro data [36] (link), Supporting Information
In our analysis of cAF-related cellular remodeling, we use the following three biomarkers:
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