Constancy and variability of contractile efficiency as a function of calcium and cross-bridge kinetics: simulation

Model Status

This model is known to run in both OpenCell and COR. It recreates the published results for the simulation, except in the case of FTI_end, FLA_max and ATP, because CellML cannot compute finite integrals or maximums of functions. These values are instead estimated based on graphs, but must be re-estimated for different initial conditions. The parameters for this model are the control values.

Model Structure

Abstract: We simulated myocardial Ca2+ (Ca) and cross-bridge (CB) kinetics to get insight into the experimentally observed constancy and variability of cardiac contractile efficiency in generating total mechanical energy under various inotropic and pathological conditions. The simulation consisted of a Ca transient, Ca association and dissociation rate constants of troponin C, and CB on and off rate constants. We evaluated sarcomere isometric twitch contractions at a constant muscle length. We assumed that each CB cycle hydrolyzes one ATP and that the force-length area (FLA) quantifies the total mechanical energy generated by CB cycles in a twitch contraction. FLA is a linear version of pressure-volume area, which quantifies the total mechanical energy of cardiac twitch contraction and correlates linearly with cardiac oxygen consumption (H. Suga, Physiol. Rev. 70: 247-277, 1990). The simulation shows that the contractile efficiency varies with changes in the Ca transient and Ca and CB kinetics except when they simultaneously speed up or slow down proportionally. These results point to possible mechanisms underlying the constancy and variability of cardiac contractile efficiency.

The original paper reference is cited below:

Constancy and variability of contractile efficiency as a function of calcium and cross-bridge kinetics: simulation, Hiroki Yamaguchi, Miyako Takaki, Hiromi Matsubara, Shingo Yasuhara, and Hiroyuki Suga, 1996, American Journal of Physiology, 270, H1501-1508. PubMed ID: 8967394

Schematic diagram showing the calcium kinetics between transient calcium (Ca2+), and troponin C (Tn), and cross bridge kinetics (CB).