Fatigue preconditioning increases fatigue resistance in mouse flexor digitorum brevis muscles with non‐functioning K_ATP channels

Abstract

The objective of this study was to determine how an initial fatigue bout (FAT1 at 37 ] 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. Abbreviations FAT1, first fatigue bout; FAT2, second fatigue bout; FDB, flexor digitorum brevis; FPC, fatigue pre-conditioning; IPC, ischaemic pre-conditioning; ROS, reactive oxygen species.

Changes in myoplasmic Ca2+during fatigue differ between FDB fibers, between glibenclamide-exposed and Kir6.2-/-fibers and are further modulated by verapamil

“…, ; Boudreault et al. ), including large membrane depolarization, large increases in unstimulated [Ca 2+ ]i and force resulting in apparent faster fatigue rate and lower capacity to recover following fatigue. Here, we again showed that compared to control fibers the absence of KATP channel activity resulted in significantly greater proportions of fibers with (1) decreases in tetanic [Ca 2+ ]i exceeding 0.5 μmol/L, (2) fade, and (3) complete failure to release Ca 2+ upon stimulation (the latter observed with glibenclamide‐exposed fibers).…”

“…[Ca 2+ ]i was then calculated from the ratio as previously described (Boudreault et al. ) using the following equation: where,…”

“…Data acquisition was set at 200 Hz; the 505 nm light emitted in 2 msec during excitation at 340 nm was divided by the 505 nm light emitted in 2 msec during excitation at 380 nm. [Ca 2+ ]i was then calculated from the ratio as previously described (Boudreault et al 2010) using the following equation:…”

“…Interestingly, one fatigue bout acutely increases fatigue resistance and lowers muscle dependency on the myoprotective effects of KATP channels, a phenomenon known as fatigue preconditioning (Boudreault et al. ). However, fatigue preconditioning only last three hrs; so, following any long period of muscle inactivity, KATP channels remain important for myoprotection.…”

“…During fatigue, KATP channel deficiency also leads to contractile dysfunctions, defined by Cifelli et al (2007), as any event from the generation of action potentials to the actin-myosin interaction that is depressed in a manner not associated with the normal process of fatigue, and that eventually incapacitates muscle from generating force. Interestingly, one fatigue bout acutely increases fatigue resistance and lowers muscle dependency on the myoprotective effects of KATP channels, a phenomenon known as fatigue preconditioning (Boudreault et al 2010). However, fatigue preconditioning only last three hrs; so, following any long period of muscle inactivity, KATP channels remain important for myoprotection.…”