Role of excitation-contraction coupling in muscle fatigue

The force produced by muscles declines during prolonged activity and this decline arises largely from processes within the muscle. At a cellular level the reduced force could be caused by: (a) reduced intracellular calcium release during activity; (b) reduced sensitivity of the myofilaments to calcium; or (c) reduced maximal force development. Experiments involving intracellular calcium measurements in isolated single fibres show that all 3 of the above contribute to the decline of force during fatigue. Metabolic changes associated with fatigue are probably involved in each of the 3 factors. Thus the accumulation of phosphate and protons which occur during fatigue cause a reduction in calcium sensitivity and a decline in maximal force. The cause of the reduced intracellular calcium during contractions in fatigue is less clear. During prolonged tetani the conduction of the action potential in the T-tubules appears to fail leading to reduced intracellular calcium in the central part of the muscle fibre. However, during repeated tetani there is a uniform decline of intracellular calcium across the fibre and this remains one of the least understood processes which contribute to fatigue.