FIGURE 6.

Progressive β-adrenergic challenge was simulated in both the FF and KO models [13] and recapitulate the major differences in EAD dynamics observed experimentally. (A) Both models transition to an unstable repolarization regime involving EADs. (B) Analysis of the EAD oscillations suggest the model dynamics are similar to those observed experimentally, where EAD amplitude, period and time of initiation are all increased in KO cells, while take-off potential is only slightly more positive. (C) Somewhat surprisingly, EAD initiation and the transition into the unstable regime is driven by non-equilibrium reactivation of I_Na rather than reactivation of I_CaL in both models, although this dominant role for I_Na is slightly more clear for the FF model.