Effects of stimulation frequencies on energy efficiency of a muscle fiber during contraction

Abstract

Contradictory experimental reports on the relationship between efficiency and stimulation frequency have hindered mechanistic understanding in converting neural activity into mechanical work during muscle contraction. To resolve this issue, we develop a biophysical model integrating calcium-mediated excitation with a detailed cross-bridge cycle to enable single-fiber simulations. Our model predictions indicate that the emergent shortening velocity is the primary determinant of cross-bridge efficiency: efficiency peaks at an optimal velocity and declines at higher or lower velocities, while frequency appears to exert secondary influence. Critically, the velocity yielding peak efficiency remains almost consistent across frequencies, with a slight upward shift at higher frequencies in most of our parametric studies. Interestingly, elevated inorganic phosphate ([Pi]) appears to amplify the efficiency disparity between high- and low-frequency regimes in our analysis. Our work suggests that stimulation frequency modulates efficiency predominantly through its regulation of shortening velocity, which primarily governs the kinetics of the myosin power stroke. This work may help clarify neural control of muscle energetics, and provide a quantitative foundation for studying muscle function in physiological and pathological contexts.