Recent advances in the understanding of skeletal muscle fatigue

Prolonged or repeated contractions of skeletal muscles lead to impaired muscle function, ie, fatigue develops. Fatigue may be caused by factors within the muscle cells (peripheral fatigue) and diminished activation from the central nervous system (central fatigue). The relative importance of peripheral versus central fatigue depends on the type of physical activity. Central fatigue may be more prominent in elderly subjects. Increased concentration of inorganic phosphate seems to be of major importance for acute peripheral fatigue. There is frequently a long-lasting depression of force production after fatiguing muscle activity, especially at low stimulation frequencies. This low-frequency fatigue seems to be due to structural changes in proteins involved in intracellular Ca2+ handling. Contractions in which the muscle is stretched (eccentric contractions) cause muscle weakness and damage. The initial defect induced by eccentric contractions is overstretched sarcomeres, but these appear to cause localized membrane tears that subsequently contribute to muscle weakness and damage.