Figure 9. Schematic representation of the validation method.

Starting from the SHAM model at 1 Hz we have developed nine models by introducing single fittings for LCC, SERCA and NCX (3 models), combination of those (4 models) and all the fittings plus changes in K⁺ and Na⁺ channels (1 model) and K⁺, Na⁺ and CaB channels (1 model). For each of the nine models we have then performed parameter swaps of the most important protein parameters: g _SERCA, K _SERCA, J _L, J _R, g _CaB, g _SRl, g _t, g _NCX, g _pCa, g _BK, g _BNa, g _K1, g _Na, g _ss, NaK_max, B _CMDN and B _TRPN. The same process was repeated at 6 Hz. All developed models, representing 5814 parameter combinations (18 models × 17 parameters × 19 values) were run to steady state. For each model we have recorded PCa, DCa, RT₅₀ and T _peak. Ultimately, we have observed the number of combinations for which simulated PCa, DCa, RT₅₀ and DCa fall within 20% variability of those four experimentally measured metrics. [Color figure can be viewed at wileyonlinelibrary.com]