MECHANISMS UNDERLYING THE REDUCTION OF ISOMETRIC FORCE IN SKELETAL-MUSCLE FATIGUE

A decline of isometric force production is one characteristic of skele tal muscle fatigue. In fatigue produced by repeated short tetani, this force decline can be divided into two components: a reduction of the cross-bridges' ability to generate force, which comes early; and a red uction of the sarcoplasmic reticulum Ca2+ release, which develops late in fatigue. Acidification due to lactic acid accumulation has been co nsidered as an important cause of the reduced cross-bridge force produ ction. However, in mammalian muscle it has been shown that acidificati on has little effect on isometric force production at physiological te mperatures. By exclusion, in mammalian muscle fatigue, the reduction o f force due to impaired cross-bridge function would be caused by accum ulation of inorganic phosphate ions, which results from phosphocreatin e breakdown. The reduction of sarcoplasmic reticulum Ca2+ release in l ate fatigue correlates with a decline of ATP and we speculate that the reduced Ca2+ release is caused by a local increase of the ADP/ATP rat io in the triads.