Hessel Anthony L, Monroy Jenna A, Nishikawa Kiisa C
Institute of Physiology II, University of Muenster, Muenster, Germany.
W.M. Keck Science Department, Claremont Colleges, Claremont, CA, United States.
Front Physiol. 2021 Mar 29;12:648019. doi: 10.3389/fphys.2021.648019. eCollection 2021.
The sliding filament-swinging cross bridge theory of skeletal muscle contraction provides a reasonable description of muscle properties during isometric contractions at or near maximum isometric force. However, it fails to predict muscle force during dynamic length changes, implying that the model is not complete. Mounting evidence suggests that, along with cross bridges, a Ca-sensitive viscoelastic element, likely the titin protein, contributes to muscle force and work. The purpose of this study was to develop a multi-level approach deploying stretch-shortening cycles (SSCs) to test the hypothesis that, along with cross bridges, Ca-sensitive viscoelastic elements in sarcomeres contribute to force and work. Using whole soleus muscles from wild type and mice, which carry a small deletion in the N2A region of titin, we measured the activation- and phase-dependence of enhanced force and work during SSCs with and without doublet stimuli. In wild type muscles, a doublet stimulus led to an increase in peak force and work per cycle, with the largest effects occurring for stimulation during the lengthening phase of SSCs. In contrast, muscles showed neither doublet potentiation features, nor phase-dependence of activation. To further distinguish the contributions of cross bridge and non-cross bridge elements, we performed SSCs on permeabilized psoas fiber bundles activated to different levels using either [Ca] or [Ca] plus the myosin inhibitor 2,3-butanedione monoxime (BDM). Across activation levels ranging from 15 to 100% of maximum isometric force, peak force, and work per cycle were enhanced for fibers in [Ca] plus BDM compared to [Ca] alone at a corresponding activation level, suggesting a contribution from Ca-sensitive, non-cross bridge, viscoelastic elements. Taken together, our results suggest that a tunable viscoelastic element such as titin contributes to: (1) persistence of force at low [Ca] in doublet potentiation; (2) phase- and length-dependence of doublet potentiation observed in wild type muscles and the absence of these effects in muscles; and (3) increased peak force and work per cycle in SSCs. We conclude that non-cross bridge viscoelastic elements, likely titin, contribute substantially to muscle force and work, as well as the phase-dependence of these quantities, during dynamic length changes.
骨骼肌收缩的滑动细丝-摆动横桥理论对最大等长力或接近最大等长力时的等长收缩过程中的肌肉特性给出了合理描述。然而，它无法预测动态长度变化期间的肌肉力量，这意味着该模型并不完整。越来越多的证据表明，除了横桥之外，一种对钙敏感的粘弹性元件（可能是肌联蛋白）也对肌肉力量和功有贡献。本研究的目的是开发一种多层次方法，利用拉伸-缩短周期（SSC）来检验以下假设：除了横桥之外，肌节中对钙敏感的粘弹性元件也对力量和功有贡献。我们使用野生型和在肌联蛋白的N2A区域有小缺失的小鼠的完整比目鱼肌，测量了在有和没有双重刺激的SSC期间增强的力量和功的激活依赖性和相位依赖性。在野生型肌肉中，双重刺激导致每个周期的峰值力量和功增加，在SSC的延长阶段进行刺激时效果最为显著。相比之下，缺失肌联蛋白的小鼠肌肉既没有双重增强特征，也没有激活的相位依赖性。为了进一步区分横桥和非横桥元件的贡献，我们对使用[Ca]或[Ca]加肌球蛋白抑制剂2,3-丁二酮单肟（BDM）激活到不同水平的通透腰大肌纤维束进行了SSC。在从最大等长力的15%到100%的激活水平范围内，与单独使用[Ca]时在相应激活水平下相比，[Ca]加BDM处理的纤维每个周期的峰值力量和功都有所增强，这表明对钙敏感的、非横桥的粘弹性元件有贡献。综上所述，我们的结果表明，诸如肌联蛋白这样的可调粘弹性元件有助于：（1）双重增强中低[Ca]时力量的持续性；（2）野生型肌肉中观察到的双重增强的相位和长度依赖性以及缺失肌联蛋白的小鼠肌肉中不存在这些效应；（3）SSC中每个周期峰值力量和功的增加。我们得出结论，在动态长度变化期间，非横桥粘弹性元件（可能是肌联蛋白）对肌肉力量和功以及这些量的相位依赖性有很大贡献。
