Thick-Filament Extensibility in Intact Skeletal Muscle
Thick-Filament Extensibility in Intact Skeletal Muscle
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DOI：
10.1016/j.bpj.2018.08.038
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发表时间：
2018-10-16
影响因子：
3.4
通讯作者：
Irving, Thomas
中科院分区：
文献类型：
--
作者：
Ma, Weikang;Gong, Henry;Irving, Thomas
肌丝伸展性是解释横纹肌肌球蛋白跨桥动力学的关键结构参数。以前的研究报告了更高的粗丝在低张力下的延展性比更好地了解和常用的值在高张力，但在解释肌肉的力学研究，一个单一的值粗丝延展性通常被假定。在这里，我们建立了完整的厚丝力延伸曲线，积极收缩，完整的脊椎动物骨骼肌。为了获得广泛的强直力，除了从未经处理的肌肉的强直收缩获得的较高张力之外，还使用肌球蛋白抑制剂blebistatin来诱导低强直力。我们发现，厚长丝的力/延伸率曲线是非线性的，所以假设一个单一的值在所有的力水平的厚长丝延伸率是不合理的。我们还表明，无论张力是被动地由肌节拉伸或主动地由跨桥产生，粗丝的可伸展性是非线性的。然而，只有在钙激活条件下产生主动张力时，肌球蛋白头的周期性才会发生变化。因此，骨骼肌中的非线性粗丝力-伸展曲线反映了对肌联蛋白基力或肌动球蛋白基力的纯粹被动反应，并且它不包括粗丝激活机制。相比之下，肌球蛋白头部周期性的转变，以积极的配置似乎只发生在响应增加主动力时，钙。
Myofilament extensibility is a key structural parameter for interpreting myosin cross-bridge kinetics in striated muscle. Previous studies reported much higher thick-filament extensibility at low tension than the better-known and commonly used values at high tension, but in interpreting mechanical studies of muscle, a single value for thick-filament extensibility has usually been assumed. Here, we established the complete thick-filament force-extension curve from actively contracting, intact vertebrate skeletal muscle. To access a wide range of tetanic forces, the myosin inhibitor blebbistatin was used to induce low tetanic forces in addition to the higher tensions obtained from tetanic contractions of the untreated muscle. We show that the force/extensibility curve of the thick filament is nonlinear, so assuming a single value for thick-filament extensibility at all force levels is not justified. We also show that independent of whether tension is generated passively by sarcomere stretch or actively by cross-bridges, the thick-filament extensibility is nonlinear. Myosin head periodicity, however, only changes when active tension is generated under calcium-activated conditions. The nonlinear thick-filament force-extension curve in skeletal muscle, therefore, reflects a purely passive response to either titin-based force or actomyosin-based force, and it does not include a thick-filament activation mechanism. In contrast, the transition of myosin head periodicity to an active configuration appears to only occur in response to increased active force when calcium is present.