Functional significance of Ca2+ in long-lasting fatigue of skeletal muscle

Repeated activation of skeletal muscle causes fatigue, which involves a red uced ability to produce force and slowed contraction regarding both the spe ed of shortening and relaxation. One important component in skeletal muscle fatigue is a reduced sarcoplasmic reticulum (SR) Ca2+ release. In the pres ent review we will describe different types of fatigue-induced inhibition o f SR Ca2+ release. We will focus on a type of long-lasting failure of SR Ca 2+ release which is called low-frequency fatigue, because this type of fati gue may be involved in the muscle dysfunction and chronic pain experienced by computer workers. Paradoxically it appears that the Ca2+ released from t he SR, which is required for contraction, may actually be responsible for t he failure of SR Ca2+ release during low-frequency fatigue. We will also di scuss the relationship between gross morphological changes in muscle fibres and long-lasting failure of SR Ca2+ release. Finally, a model linking musc le cell dysfunction and muscle pain is proposed.