Figure 6.

The experimental and simulated effects of ryanodine and nifedipine on the cytosolic Ca²⁺ signals. (A) Average cytosolic Ca²⁺ was recorded from a single cardiomyocyte during 1-Hz pacing using the line-scan method (left). The middle panel shows the Ca²⁺ signal from the same cell after 5 min perfusion of ryanodine (50 μM). After this, the ryanodine perfusion was continued with nifedipine (10 μM), and after 1 min of perfusion, the Ca²⁺ signal was recorded from the same cell (right). The average value of the initial slope of the Ca²⁺ transient (dashed gray line) in control conditions and after exposure to ryanodine (right, n = 14, ^∗∗p < 0.01). (B) The experiment was reproduced by simulation with the model (see Methods). The effects of ryanodine and ryanodine + nifedipine were simulated with the D_Ca fitted to our data (normal, solid line) and with the D_Ca in water (reduced, dash-dotted line). The figure shows the average cytosolic Ca²⁺ from the simulations. (C) The simulated data with normal D_Ca (solid gray bars) and with reduced D_Ca (gray-hatched bars) and the average experimental data (black bars) from the experiments (n = 14). The left panels show the Ca²⁺-transient amplitude and decay in control conditions and after exposure to ryanodine. The upper right panel shows the diastolic [Ca²⁺]_i in control, with ryanodine, and with ryanodine + nifedipine. The lower right panel shows the simulated diastolic SR Ca²⁺ content in cytosol volume in control, ryanodine, and ryanodine + nifedipine conditions.