FIGURE 8.

Time-dependent behavior of Ca²⁺ and NADH after changes in workload. (A, B) Experimental data showing the responses of NADH (A) and mitochondrial Ca²⁺ (B) to an increase in stimulation frequency from 0.25 to 2 Hz in a rat cardiac trabeculae (Reproduced from Brandes and Bers (2002) by copyright permission of the Biophysical Society). (C) Model response of mitochondrial Ca²⁺ to the pacing protocol described in Model Building and Numerical Methods, applied at low frequency (0.25 Hz) for 100 s, and then a high frequency (2 Hz) for 200 s, followed by a return to the low frequency. (D) Time course of NADH levels during changes in pacing frequency, simulated by increasing the Ca²⁺ pulse frequency combined with an increase in ADP_i. The “pull” parametric condition is similar to that defined in the legend of Fig. 5 except for ρ^RES = 0.0006, ρ^F1 = 1.787 mM, and mM s⁻¹; “pull II” is similar to “pull” except ρ^RES = 0.00072 mM and mM s⁻¹. (E) The effects of a change in Ca²⁺ pulse frequency or ADP_i applied separately.