Simulation of steady state and transient cardiac muscle response experiments with a Huxley-based contraction model

Abstract

A cardiac muscle model is presented with the purpose of representing a wide range of mechanical experiments at constant and transient Ca 2+ concentration. Modifications of a previous model were: weak and power attached crossbridge states, a troponin system involving three consecutive regulatory troponin–tropomyosin units acting together in Ca 2+ kinetics and detachment constants depending on crossbridge length. This model improved cooperativity (Hill coefficient close to 4) and the force–velocity relationship, and incorporated the representation of the four phases of muscle response to length and force steps, isotonic shortening and isosarcometric contractions, preserving previous satisfactory results. Moreover, experimentally reported effects, such as length dependence on Ca 2+ affinity, the decreased cooperativity at higher Ca 2+ concentrations, temperature effects on the stiffness–frequency relationship and the isometric internal shortening due to series elasticity, were obtained. In conclusion, the model is more comprehensive than a previous version because it is able to represent a wider variety of steady state experiments, the mechanical variables in twitches can be adequately related to intracellular Ca 2+, and all the simulations were performed with the same set of parameters.