The effects of the myosin-II inhibitor N-benzyl-p-toluene sulphonamide on fatigue in mouse single intact toe muscle fibres

Aim: This study determined whether fatigue in skeletal muscle is primarily due to the repeated elevations of myoplasmic free calcium concentration ([Ca2+](i)) or to metabolite accumulation. Methods: We examined the effects of N-benzyl-p-toluene sulphonamide (BTS) which is a potent and specific inhibitor of fast muscle myosin-II on the development of fatigue in mouse flexor digitorum brevis (FDB) muscle fibres. Single intact FDB fibres were micro-injected with indo-1. to monitor changes in [Ca2+](i) and stimulated repeatedly for a maximum of 150 tetani or until force declined to 40%. Results: BTS markedly reduced tetanic force but had no effect on the tetanic [Ca2+](i) transients. When fatigue was induced in the presence of BTS, the reduction in [Ca2+](i) and force transients occurred much more slowly than in the absence of BTS. The extent of force depression was similar after induction of fatigue in fibres exposed to Tyrode only or to BTS and force recovered to the same extent. Conclusion: The results suggest that the decrease in tetanic [Ca2+](i) and force caused during fatigue are due mainly to accumulated metabolic changes.