Why can a working muscle produce less force over time?

Muscle fatigue is an activity-related decline in the ability to produce force or power. It can develop while a muscle continues receiving signals and using ATP. The result depends on the whole route from nervous-system activation to the contractile machinery inside fibers, rather than on filament sliding alone.

One contribution is central: the nervous system may provide less effective drive to motor units. Feedback from working muscles interacts with the pathways producing that drive. Another contribution is peripheral, arising in the muscle and its activation processes. Changes in electrical excitation, calcium release or the response of contractile proteins can reduce the force a fiber produces.

During demanding activity, ATP must be replenished rapidly. Changes in metabolites, including inorganic phosphate and hydrogen ions, can affect calcium handling and actin–myosin force production. Lactate accumulation is not a complete explanation of fatigue. The effects of acidity, other metabolites and neural changes must be distinguished, and their importance varies with the task and its duration.

These contributions interact, and their relative importance changes between brief intense activity and longer sustained work. Less force can become available through changes at more than one point along the pathway. A complete explanation therefore has to consider both activation of the muscle and what happens inside its fibers.