Aims: 

The present study was conducted in order to test the hypothesis that differences in reactive oxygen species (ROS) metabolism are responsible for different causes of decreased force at low frequencies (i.e. decreased SR Ca²⁺release vs. reduced myofibrillar Ca²⁺sensitivity). Methods:

Intact, single muscle fibres were dissected from flexor digitorum brevis muscles of rats and mice (wildtype and superoxide dismutase (SOD2) overexpressing). Force and myoplasmic free [Ca²⁺] ([Ca²⁺]_i) were measured. Fibres were stimulated at frequencies varying from 15 to 100 Hz before and 30 min after fatigue induced by repeated tetani (70 Hz, 350 ms). Results:

Force was markedly decreased (~60-70%, P < 0.05) at low stimulation frequencies 30 min after fatiguing stimulation in all fibres. This reduction was associated with reduced tetanic [Ca²⁺]_i in wildtype mouse fibres (to 64 ± 11% of the original, P < 0.05), which can not be reversed by application of the reducing agent dithiothreitol or the antioxidant N-acetylcysteine. In contrast, rat fibres and mouse SOD2 overexpressing fibres showed a significant (P < 0.05) decreased myofibrillar Ca²⁺sensitivity (assessed by measuring the [Ca²⁺]_i required to produce 50% of the maximal tetanic force), which can be partially reversed by application of the reducing agent dithiothreitol.

Conclusion: 

In conclusion, the origin of the delayed force recovery seems to depend on the ROS metabolism. These findings may have clinical implications since ROS-mediated impairments in myofibrillar function can be counteracted by reductants and antioxidants, whereas changes in SR Ca²⁺handling appear more robust.