Role of phosphate and calcium stores in muscle fatigue

Intensive activity of muscles causes a decline in performance, known as fat igue, that is thought to be caused by the effects of metabolic changes on e ither the contractile machinery or the activation processes. The concentrat ion of inorganic phosphate (P-i) in the myoplasm ([P-i](myo)) increases sub stantially during fatigue and affects both the myofibrillar proteins and th e activation processes. It is known that a failure of sarcoplasmic reticulu m (SR) Ca2+ release contributes to fatigue and in this review we consider h ow raised [P-i](myo) contributes to this process. Initial evidence came fro m the observation that increasing [P-i](myo) causes reduced SR Ca2+ release in both skinned and intact fibres. In fatigued muscles the store of releas able Ca2+ in the SR declines mirroring the decline in SR Ca2+ release. In m uscle fibres with inoperative creatine kinase the rise of [P-i](myo) is abs ent during fatigue and the failure of SR Ca2+ release is delayed. These res ults can all be explained if inorganic phosphate can move from the myoplasm into the SR during fatigue and cause precipitation of CaPi within the SR. The relevance of this mechanism in different types of fatigue in humans is considered.