Figure 7.

Simulation study. (A) APD restitution curves showing the reliance on substrate modification for alternans promotion. Full remodelling (A1) as well as J_rel and CSQN modification (A2) result in APD alternans across the same cycle lengths (bifurcation of the red line), while modifications of only CSQN (A3) or J_rel (A4) does not promote APD alternans. (B) Comparison of AP and Ca²⁺ transient from single cell simulation (B1) and tissue simulation (B2) showing that alternans is preserved in tissue. B3: results of the two-dimensional tissue simulation: a patch of alternans-susceptible cells (patch A, delimited by a white dashed line) surrounded by a larger patch of alternans-resistant cells (patch B) is show for two consecutive beats (beat number 94 and 95). Red and blue represent short and long APD, respectively. A change in APD between the two consecutive beats is observed within the patch of alternans-susceptible cells (Patch A, with red turning light blue) but not in the patch of alternans-resistant cells (Patch B, with blue remaining blue). On the right, action potential traces for both beats from patch A (top) and B (bottom) show that alternans only appears within the patch of alternans-susceptible cells (ΔAPD = 11 ms). APD, action potential duration; CSQN, Calsequestrin; J_rel, sarcoplasmic Ca²⁺ release (flux).