Powers Krysta, Schappacher-Tilp Gudrun, Jinha Azim, Leonard Tim, Nishikawa Kiisa, Herzog Walter
Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, AB, Canada, T2N 1N4.
Department for Mathematics and Scientific Computing, NAWI Graz, Karl-Franzens-University Graz, A-8010 Graz, Austria.
J Exp Biol. 2014 Oct 15;217(Pt 20):3629-36. doi: 10.1242/jeb.105361. Epub 2014 Aug 21.
The sliding filament theory of muscle contraction is widely accepted as the means by which muscles generate force during activation. Within the constraints of this theory, isometric, steady-state force produced during muscle activation is proportional to the amount of filament overlap. Previous studies from our laboratory demonstrated enhanced titin-based force in myofibrils that were actively stretched to lengths which exceeded filament overlap. This observation cannot be explained by the sliding filament theory. The aim of the present study was to further investigate the enhanced state of titin during active stretch. Specifically, we confirm that this enhanced state of force is observed in a mouse model and quantify the contribution of calcium to this force. Titin-based force was increased by up to four times that of passive force during active stretch of isolated myofibrils. Enhanced titin-based force has now been demonstrated in two distinct animal models, suggesting that modulation of titin-based force during active stretch is an inherent property of skeletal muscle. Our results also demonstrated that 15% of the enhanced state of titin can be attributed to direct calcium effects on the protein, presumably a stiffening of the protein upon calcium binding to the E-rich region of the PEVK segment and selected Ig domain segments. We suggest that the remaining unexplained 85% of this extra force results from titin binding to the thin filament. With this enhanced force confirmed in the mouse model, future studies will aim to elucidate the proposed titin-thin filament interaction in actively stretched sarcomeres.
肌肉收缩的滑动丝理论被广泛认为是肌肉在激活过程中产生力量的方式。在该理论的框架内，肌肉激活过程中产生的等长稳态力与细丝重叠量成正比。我们实验室之前的研究表明，在被主动拉伸至超过细丝重叠长度的肌原纤维中，基于肌联蛋白的力量增强。这一观察结果无法用滑动丝理论来解释。本研究的目的是进一步探究主动拉伸过程中肌联蛋白的增强状态。具体而言，我们证实了在小鼠模型中观察到了这种增强的力量状态，并量化了钙对这种力量的贡献。在分离的肌原纤维的主动拉伸过程中，基于肌联蛋白的力量增加至被动力量的四倍之多。现在已在两种不同的动物模型中证明了基于肌联蛋白的力量增强，这表明主动拉伸过程中基于肌联蛋白的力量调节是骨骼肌的固有特性。我们的结果还表明，肌联蛋白增强状态的15%可归因于钙对该蛋白质的直接作用，推测是钙与PEVK段富含E的区域以及选定的免疫球蛋白结构域段结合后蛋白质发生了硬化。我们认为，这种额外力量中其余无法解释的85%是由于肌联蛋白与细肌丝结合所致。在小鼠模型中证实了这种增强的力量后，未来的研究将旨在阐明主动拉伸的肌节中所提出的肌联蛋白-细肌丝相互作用。
