A computational model for temperature effects on myofilament dynamics in rodent ventricular myocytes

Purpose Cardiac muscle contraction and relaxation depends on sequential mechanisms: for contraction, increase in cytosolic Ca 2+ concentration triggers actin-myosin interaction, while for relaxation the removal of cytosolic Ca²⁺ leads to detachment of myosin cross-bridges from actin in the myofilaments. As most experimental studies are carried out at sub-physiological temperatures, and both Ca 2+ transport and myofilament function are differently affected by temperature, it is important to understand how temperature impacts the contraction force and the relaxation rate. Methods To investigate this dynamic, a new model of myofilament kinetics is proposed, in which a pre-existing myofilament model coupled with an electrophysiological model of rodent ventricular myocytes was calibrated using experimental data from the literature. The model incorporates the Q 10 coefficient into the seven parameters that determine the transition rates between myofilament kinetic states, allowing simulation of contractile force at different temperatures. Results The new model successfully replicated the nonlinear dependence of the developed force on temperature, as well as the monotonic acceleration of relaxation in response to a rise in temperature from 22.5 °C to 37.5 °C, observed experimentally in rodent myocardium. The use of a population simulation method demonstrated a contractile behavior qualitatively similar to experimental observations. Finally, the model reproduced the relationship between temperature and myofilament Ca²⁺ sensitivity reported experimentally. Conclusion The present computational model effectively simulates the influence of temperature on myofilament dynamics and force development by ventricular myocytes of rodents.