Computational Model of Cellular Metabolic Dynamics in Skeletal Muscle Fibers during Moderate Intensity Exercise

Human skeletal muscles have different fiber types with distinct metabolic functions and physiological properties. The quantitative metabolic responses of muscle fibers to exercise provide essential information for understanding and modifying the regulatory mechanisms of skeletal muscle. Since in vivo data from skeletal muscle during exercise is limited, a computational, physiologically based model has been developed to quantify the dynamic metabolic responses of many key chemical species. This model distinguishes type I and II muscle fibers, which share the same blood supply. An underlying hypothesis is that the recruitment and metabolic activation of the two main types of muscle fibers differ depending on the pre-exercise state and exercise protocols. Here, activation measured by metabolic response (or enzymatic activation) in single fibers is considered linked but distinct from fiber recruitment characterized by the number (or mass) of each fiber type involved during a specific exercise. The model incorporates species transport processes between blood and muscle fibers and most of the important reactions/pathways in cytosol and mitochondria within each fiber type. Model simulations describe the dynamics of intracellular species concentrations and fluxes in muscle fibers during moderate intensity exercise according to various experimental protocols and conditions. This model is validated by comparing model simulations with experimental data in single muscle fibers and in whole muscle. Model simulations demonstrate that muscle-fiber recruitment and metabolic activation patterns in response to exercise produce significantly distinctive effects depending on the exercise conditions.