Mechanisms underlying the slow recovery of force after fatigue:: importance of intracellular calcium

Recovery of force production after an intense bout of activity may sometimes take several days, especially at low activation frequencies ('low frequency fatigue'). This slow recovery can also be observed in isolated muscle and single muscle fibres. The origin of the force deficit is failure of excitation-contraction coupling at the level of the triads. The most likely cause of the failure is an elevated intracellular Ca2+ level, but the site of action of Ca2+ is unclear. Available evidence does not support the involvement of Ca2+-activated proteases. Ca2+-induced damage to mitochondria or swelling of t-tubules do not seem to be causative factors. Other mechanisms are discussed, including possible detrimental effects of Ca2+-activated lipases, calmodulin, and reactive oxygen species.