Figure 7
Comparison of experimental data and simulated results of WT and CaMK. Black (squares), red (circles) and green (triangles) symbols indicate WT, CaMK overexpression (CaMK3X) and CaMK overexpression with no compensations (CaMK3X*), respectively. The corresponding test cases without and with CaMK induced SR leak are depicted with closed symbols & continuous lines and open symbols & dashed lines. (A) CaMK activity as a function of pacing frequency. The pacing-induced (0.5 to 4 Hz) increase of CaMK activity is 35% smaller for CaMK3X vs. WT. (B) and (C) [Car+]i transient at 1 Hz. Compared to WT, the amplitude of the measured [20] and the simulated transient changes by -77% and -62% due to CaMK overexpression, respectively, and CaMK3X* by +117%. (D) Time constants of the [Ca2+]i transient decay. At 1 Hz, the combination of CaMK overexpression and compensational changes increases the time constant of measured [20] and simulated Ca2+ transient decay by 7.8% and 14%, respectively. Whereas, the mere overexpression (CaMK3X*) decreases Ï„Ca by 41% compared to WT. (E) Peak value of SR calcium release as function of pacing frequency. WT and CaMK3X were not affected to a large extent by the leakiness of RyR. Whereas, in the CaMK3X* test case, the behaviour changes strikingly. (F) and (G) The amplitudes of Ca2+ transient and contractile force as a function of pacing frequency. A "leaky" RyR tends to normalize the functionality of the CaMK3X* test case, but has little effect in WT and CaMK3X. (H) Activity of CaN as a function of pacing frequency. At 1 Hz pacing, CaN activity for CaMK3X is reduced to 10% of the WT value and increased by 69% for CaMK3X*. Increased pacing is unable restore CaN of CaMK3X to the WT level, whereas the deviation of CaMK3X* from WT is reversed by faster pacing. Interestingly, the RyR leakiness brings the CaN-frequency curve of CaMK3X* closer to WT.