Illustration of cAF-remodeling processes accounted for in the model and consequent changes in electrophysiological properties and Ca<sup>2+</sup> dynamics.

<p>(A) Schematic presentation of the cell model. Ionic currents and ion concentrations are referred to with I<sub>X</sub> and [X<sup>z</sup>]<sub>compartment</sub>, respectively. Furthermore, NKA =  sodium potassium ATPase, NCX =  sodium Ca<sup>2+</sup> exchanger, PMCA =  plasma membrane Ca<sup>2+</sup> ATPase, SERCA =  sarcoplasmic reticulum Ca<sup>2+</sup> ATPase, PLB =  phospholamban, SLN =  sarcolipin and CRU =  calcium release unit or ryanodine receptor. Colour coding with red and blue refers to increased and decreased activity and/or expression of cellular components (proteins involved in ion transport), respectively. (B & C) cAF-remodeling shortens the AP and hyperpolarizes the membrane. Simulation results are compared to <i>in vitro</i> findings of Yu et al. <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003620#pcbi.1003620-Yu2" target="_blank">[42]</a> and Dobrev et al. <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003620#pcbi.1003620-Dobrev3" target="_blank">[43]</a>. (D & E) cAF-remodeling decreases the amplitude of CaT, diastolic Ca<sup>2+</sup> concentration and SR Ca<sup>2+</sup> content, corresponding to <i>in vitro</i> results of Voigt et al. <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003620#pcbi.1003620-Voigt2" target="_blank">[21]</a> (cyan bar), Voigt et al. <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003620#pcbi.1003620-Voigt1" target="_blank">[14]</a> (red bar), Wakili et al. <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003620#pcbi.1003620-Wakili1" target="_blank">[10]</a> (diastolic Ca<sup>2+</sup>) and Grandi et al. <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003620#pcbi.1003620-Grandi1" target="_blank">[11]</a> (CaT<sub>amp</sub> and SR Ca<sup>2+</sup> content). (F & G) Spatiotemporal view of the CaT along the radial direction of the virtual cell in nSR and cAF (x =  distance from sarcolemma).</p>