Analyzing the Functional Properties of the Creatine Kinase System with Multiscale ‘Sloppy’ Modeling
Figure 4
Prediction of energy transport from mitochondria to cytosol by PCr.
(A) Forcing function of pulsatile cytosolic ATP hydrolysis for the last two cardiac cycles of a simulation over 60 s. (B) Prediction of the relative PCr contribution to high-energy phosphate flux across the mitochondrial outer membrane (Rdiff,PCr) at heart rate 220 bpm. The shaded region gives the central 95% confidence interval of the Rdiff,PCr trajectories derived from ensemble simulations of 658 parameter sets. Solid lines depict a single simulation of the best scoring parameter set. Blue color indicates the condition with CK active. Simulations with CK inhibited by 98% by IA are plotted in orange. Note that two cardiac cycles are plotted after a steady state was reached.