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 (Ca(2+)) 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 Ca(2+) 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 Ca(2+) transients. When fatigue was induced in the presence of BTS, the reduction in Ca(2+) 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 Ca(2+) and force caused during fatigue are due mainly to accumulated metabolic changes.