Figure 6
Comparison of WT and transgenic LCC models. The results of TG models with constitutively active CaMK-dependent phosphorylation (cLCC) and blocked phosphorylation (bLCC) of LCC are depicted with red circles and blue triangles, respectively. These are compared to simulation results of wild-type model (black squares). (A) Peak value of L-type calcium current (ICa, L) as a function of pacing frequency. The ICa, L peak amplitude of bLCC model deviates rather little from the WT (-4.3% at 4 Hz). In the cLCC model, the peak value of ICa, L is larger than in the WT (+7.5% at 0.5 Hz pacing), but the deviation decreases as pacing frequency increases. (B) Action potential duration (90% recovery, APD90) presented as a function of pacing frequency. Compared to WT, the APD90 is virtually unchanged in both TG models. (C) Contraction force amplitude as a function of pacing frequency. The difference in the force amplitude is also very small: -4.9% for bLCC (at 4 Hz) and +14% for cLCC (at 0.5 Hz). Inset shows twitch force of the WT and TG model at 0.5 Hz and 4 Hz pacing frequencies. (D) and (E) SR Ca2+ content ([Ca2+]SR) and the integral of Ca2+ release from the SR (Jrel) during one AP plotted as a function of pacing frequency. There is very little change in the [Ca2+]SR at low pacing frequencies. The maximum deviation from WT is seen at 4 Hz pacing: -6% and +5% for bLCC and cLCC, respectively. The integral of Jrel changes slightly more -9% and +7% for bLCC and cLCC, respectively. (F) Demonstration of the autoregulation involving ICa, L and Jrel. Dashed lines present acute transgenic situation, in which the LCC inactivation is calculated from the WT parameter values. Note that the time axis of the traces has been shifted for easier comparison.