Figure 5

Comparison of experimental data and simulated results of WT and PLB knockout. Results of WT, PLB knockout and PLB knockout without compensation are shown with black, red and green symbols, respectively. (A) and (B) Two postrest Ca²⁺ transients from experimental [32] and simulated data are shown. There is a marked similarity of the shapes of the corresponding Ca²⁺ transients of the simulated results and the measurements, e.g., the amplitude ratio of PLB-KO vs. WT is 1.6 in both the in vivo and the in silico experiments. The amplitude of the Ca²⁺ transient is a further 12% larger in the PLB-KO* test case (knockout with no compensations). (C) Amount of active CaMK and CaN as a function of pacing frequency. Compared to WT the mean activities of CaMK and CaN increase by 35% and 102% for PLB-KO, and by 44% and 122% for PLB-KO* at 0.5 Hz pacing. These deviations from behaviour of the WT myocyte are attenuated when the pacing frequency is increased. (D) Time constants of the [Ca²⁺]_i transient decay. Measured data [19] is compared to simulated results at 0.5 Hz. The value of τ is decreased by 26% and 28% compared to WT for the PLB-KO and PLB-KO* simulations, respectively, and by 40% in the experiments of Li et al. [19]. (E) SR Ca²⁺ content calculated from measured data [19] and simulated results at 0.5 Hz. The increases of [Ca²⁺]_SR appears to be exaggerated in silico. However, an earlier report by Chu et al. [33] showed an 86% increase of [Ca²⁺]_SR in the PLB-KO mouse myocytes compared to WT. Thus, the model prediction of the SR calcium content is in good qualitative agreement with the experiments.