Fatigue preconditioning increases fatigue resistance in mouse flexor digitorum brevis muscles with non-functioning...

The objective of this study was to determine how an initial fatigue bout (FAT1 at 37°C) affects free myoplasmic Ca(2+) concentration and force ([Ca(2+)](i)/force) during a subsequent fatigue bout (FAT2) in mouse flexor digitorum brevis (FDB). During FAT1, both tetanic [Ca(2+)](i)/force decreased; however, they decreased to significantly lower levels when FAT1 was carried out in the presence of glibenclamide, a sarcolemmal K(ATP) (sK(ATP)) channel blocker. Glibenclamide also elicited greater increases in unstimulated [Ca(2+)](i)/force, which occurred when fibres failed to fully relax between contractions during FAT1. Finally, glibenclamide impaired force recovery after FAT1. The decreases in tetanic [Ca(2+)](i)/force and increases in unstimulated [Ca(2+)](i)/force were slower during FAT2 elicited 60 min after FAT1. Under control conditions, the effects were small with very few significant differences. In the presence of glibenclamide, on the other hand, the differences between FAT1 and FAT2 were very large. Unexpectedly, the differences in unstimulated and tetanic [Ca(2+)](i)/force between control and glibenclamide conditions observed during FAT1 were no longer observed during FAT2. The lack of differences was not related to a failure of glibenclamide to block K(ATP) channels during FAT2 because the effects of FAT1 on FAT2 were also observed using Kir6.2(-/-) mouse FDB, which lack sK(ATP) channel activity. The differences in [Ca(2+)](i)/force between FAT1 and FAT2 could be observed with FAT1 duration of just 30 s and a FAT1-FAT2 interval of at least 30 min. A modulation of factors involved in ischaemic pre-conditioning, i.e. A1-adenosine receptors, sK(ATP) and mitochondrial K(ATP) (mK(ATP)) channels, PKC and reactive oxygen species, during FAT1 had no effect on FAT2 fatigue kinetics. It is concluded that a preceding fatigue bout triggers an acute physiological process that prevents the contractile dysfunction induced by non-functioning K(ATP) channels.