Figure 5.

Ionic mechanisms of repolarization dynamics during verapamil application. (A) Baseline model. (B) Multi-variable optimized model. Verapamil (simulated as a scaling of G_CaL by 0.64, a scaling of G_Kr by 0.55, and a scaling of G_Na by 0.998) decrease I_Kr by similar amounts in the baseline and in the multi-variable optimized models. However, due to the up-regulated I_CaL and I_NCX in the optimized model, it sustains a larger loss of inward current than the baseline model. Further, the increased I_Ks in this model provides a repolarization reserve. Together, these effects lead to a maintained APD₅₀ value and an only slightly increased value of APD₉₀.