Exhaustion of Skeletal Muscle Fibers Within Seconds: Incorporating Phosphate Kinetics Into a Hill-Type Model
Exhaustion of Skeletal Muscle Fibers Within Seconds: Incorporating Phosphate Kinetics Into a Hill-Type Model
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DOI：
10.3389/fphys.2020.00306
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发表时间：
2020-05-05
影响因子：
4
通讯作者：
Goetz, Thomas
中科院分区：
文献类型：
--
作者：
Rockenfeller, Robert;Guenther, Michael;Goetz, Thomas
由神经冲动和随后的钙释放引发，骨骼肌纤维收缩（主动产生力），这是肌动蛋白-肌球蛋白跨桥的重复动力冲程的结果。进行这些跨桥循环所需的能量由三磷酸腺苷（ATP）的水解提供。反应产物，腺苷二磷酸（ADP）和无机磷酸盐（Pi），然后被用于其他反应物，如磷酸肌酸，以补充ATP能量储存。然而，类似于酵母在自己的废物手中死亡，水解反应产物降低了ATP的化学势，从而抑制了肌肉的力量产生，因为它们的浓度上升。我们建议使用术语“疲惫”来表示由Pi和ADP累积沿着ATP浓度可能降低引起的力量降低（疲劳）。在生物化学动力学的基础上，我们提出了一个基于水解ATP-ADP-P-i动力学的肌纤维耗竭模型，该模型假定是长度和钙活性依赖的。写在微分代数方程方面，新的子模型允许以一种简单的方式增强现有的希尔型兴奋收缩模型。测量了家兔M.腓肠肌和M. plantaris被用于模型验证，发现我们建议的模型增强被证明是非常有前途的。我们讨论了我们的模型方法，提高肌肉模型的影响，以及一些方面的意义磷酸盐动力学作为肌肉疲劳的一个贡献者。
Initiated by neural impulses and subsequent calcium release, skeletal muscle fibers contract (actively generate force) as a result of repetitive power strokes of acto-myosin cross-bridges. The energy required for performing these cross-bridge cycles is provided by the hydrolysis of adenosine triphosphate (ATP). The reaction products, adenosine diphosphate (ADP) and inorganic phosphate (P-i), are then used-among other reactants, such as creatine phosphate-to refuel the ATP energy storage. However, similar to yeasts that perish at the hands of their own waste, the hydrolysis reaction products diminish the chemical potential of ATP and thus inhibit the muscle's force generation as their concentration rises. We suggest to use the term "exhaustion" for force reduction (fatigue) that is caused by combined P-i and ADP accumulation along with a possible reduction in ATP concentration. On the basis of bio-chemical kinetics, we present a model of muscle fiber exhaustion based on hydrolytic ATP-ADP-P-i dynamics, which are assumed to be length- and calcium activity-dependent. Written in terms of differential-algebraic equations, the new sub-model allows to enhance existing Hill-type excitation-contraction models in a straightforward way. Measured time courses of force decay during isometric contractions of rabbit M. gastrocnemius and M. plantaris were employed for model verification, with the finding that our suggested model enhancement proved eminently promising. We discuss implications of our model approach for enhancing muscle models in general, as well as a few aspects regarding the significance of phosphate kinetics as one contributor to muscle fatigue.