University of Ottawa, Department of Cellular and Molecular Medicine, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
J Physiol. 2010 Nov 15;588(Pt 22):4549-62. doi: 10.1113/jphysiol.2010.191510. Epub 2010 Sep 20.
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+)/force) during a subsequent fatigue bout (FAT2) in mouse flexor digitorum brevis (FDB). During FAT1, both tetanic Ca(2+)/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+)/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+)/force and increases in unstimulated Ca(2+)/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+)/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+)/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.
本研究旨在探讨初次疲劳（37°C 时的 FAT1）如何影响随后的疲劳（FAT2）过程中，小鼠屈趾短肌（FDB）的游离肌浆钙离子浓度和力（Ca(2+)/力）。在 FAT1 过程中，强直收缩时的 Ca(2+)/力均下降；但当 FAT1 过程中使用磺酰脲类药物（sarcolemmal K(ATP) (sK(ATP)) 通道阻滞剂）格列本脲时，下降幅度明显更大。格列本脲还会引起更大的未刺激Ca(2+)/力的增加，这是由于在 FAT1 过程中，纤维在收缩之间无法完全放松所致。最后，格列本脲会损害 FAT1 后的力恢复。在 FAT1 后 60 分钟引发的 FAT2 过程中，Ca(2+)/力的下降和未刺激Ca(2+)/力的增加均较为缓慢。在对照条件下，效果较小，仅有少数有显著差异。但另一方面，在格列本脲存在的情况下，FAT1 和 FAT2 之间的差异非常大。出乎意料的是，在 FAT1 过程中观察到的未刺激和强直收缩Ca(2+)/力的对照和格列本脲条件之间的差异，在 FAT2 过程中不再观察到。缺乏差异与格列本脲在 FAT2 过程中未能阻断 K(ATP) 通道无关，因为使用 Kir6.2(-/-) 小鼠 FDB 也观察到了 FAT1 对 FAT2 的影响，后者缺乏 sK(ATP) 通道活性。在 FAT1 持续时间仅为 30 秒且 FAT1-FAT2 间隔至少 30 分钟的情况下，可以观察到 FAT1 和 FAT2 之间的Ca(2+)/力差异。在 FAT1 过程中，对缺血预适应相关因素（即 A1-腺苷受体、sK(ATP) 和线粒体 K(ATP) (mK(ATP)) 通道、PKC 和活性氧）的调节，对 FAT2 疲劳动力学没有影响。因此，可以得出结论，先前的疲劳会引发一种急性生理过程，防止因非功能 K(ATP) 通道引起的收缩功能障碍。
