Figure 3

Examples of outputs (colour coding matches Figure 1) during a dynamic in silico pacing experiment. The simulation series was started from a steady-state (pacing at 0.5 Hz) and the pacing frequency was increased with six second intervals to 1, 2, 3, and 4 Hz. Left panel shows the L-type calcium current (I_{Ca, L}), sodium calcium exchanger current (I_NCX), and calcium concentration in the cytosol ([Ca²⁺]_i). Whereas the peak amplitude of I_{Ca, L} is hardly changed, the calcium transients become smaller as the pacing frequency increases, because the sarcoplasmic reticulum (SR) Ca²⁺ stores are reduced. At the same time, the rise of the diastolic [Ca²⁺]_i causes an increase in the diastolic outward I_NCX. In the right panel, the concentration of active calcineurin (CaN) and Ca²⁺/calmodulin-dependent protein kinase II (CaMK), as well as the calcium concentration in the network SR (Ca_JSR) and in the junctional SR (Ca_NSR), are presented from the same incremental simulation. The CaN curve follows the Ca²⁺ transients more closely, in fact oscillating clearly at the lowest pacing frequencies, whereas CaMK activity displays a stronger integrative aspect and, accordingly, a much smoother time-course.