Miller Mark S, Bedrin Nicholas G, Ades Philip A, Palmer Bradley M, Toth Michael J
Department of Molecular Physiology and Biophysics, College of Medicine, University of Vermont, Burlington, Vermont; Department of Kinesiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, Massachusetts
Department of Molecular Physiology and Biophysics, College of Medicine, University of Vermont, Burlington, Vermont;
Am J Physiol Cell Physiol. 2015 Mar 15;308(6):C473-84. doi: 10.1152/ajpcell.00158.2014. Epub 2015 Jan 7.
Skeletal muscle contractile performance is governed by the properties of its constituent fibers, which are, in turn, determined by the molecular interactions of the myofilament proteins. To define the molecular determinants of contractile function in humans, we measured myofilament mechanics during maximal Ca(2+)-activated and passive isometric conditions in single muscle fibers with homogenous (I and IIA) and mixed (I/IIA and IIA/X) myosin heavy chain (MHC) isoforms from healthy, young adult male (n = 5) and female (n = 7) volunteers. Fibers containing only MHC II isoforms (IIA and IIA/X) produced higher maximal Ca(2+)-activated forces over the range of cross-sectional areas (CSAs) examined than MHC I fibers, resulting in higher (24-42%) specific forces. The number and/or stiffness of the strongly bound myosin-actin cross bridges increased in the higher force-producing MHC II isoforms and, in all isoforms, better predicted force than CSA. In men and women, cross-bridge kinetics, in terms of myosin attachment time and rate of myosin force production, were independent of CSA, although women had faster (7-15%) kinetics. The relative proportion of cross bridges and/or their stiffness was reduced as fiber size increased, causing a decline in specific force. Results from our examination of molecular mechanisms across the range of physiological CSAs explain the variation in specific force among the different fiber types in human skeletal muscle, which may have relevance to understanding how various physiological and pathophysiological conditions modulate single-fiber and whole muscle contractility.
骨骼肌的收缩性能受其组成纤维特性的支配，而这些纤维特性又由肌丝蛋白的分子相互作用所决定。为了确定人类收缩功能的分子决定因素，我们在最大钙（Ca2+）激活和被动等长条件下，测量了来自健康年轻成年男性（n = 5）和女性（n = 7）志愿者的具有均匀（I型和IIA型）和混合（I/IIA型和IIA/X型）肌球蛋白重链（MHC）亚型的单根肌纤维中的肌丝力学。在检查的横截面积（CSA）范围内，仅含有MHC II亚型（IIA和IIA/X）的纤维比MHC I型纤维产生更高的最大钙（Ca2+）激活力，从而导致更高（24 - 42%）的比力。在产生更高力的MHC II亚型中，强结合的肌球蛋白 - 肌动蛋白横桥的数量和/或刚度增加，并且在所有亚型中，横桥比CSA能更好地预测力。在男性和女性中，就肌球蛋白附着时间和肌球蛋白力产生速率而言，横桥动力学与CSA无关，尽管女性的动力学更快（7 - 15%）。随着纤维尺寸增加，横桥的相对比例和/或其刚度降低，导致比力下降。我们对生理CSA范围内分子机制的研究结果解释了人类骨骼肌不同纤维类型之间比力的差异，这可能与理解各种生理和病理生理条件如何调节单纤维和全肌收缩性有关。
