Bates Jason H T
Vermont Lung Center, Department of Medicine, University of Vermont, Burlington, Vermont
J Appl Physiol (1985). 2015 Mar 15;118(6):684-91. doi: 10.1152/japplphysiol.00938.2014. Epub 2015 Jan 8.
Imposed length changes of only a small percent produce transient reductions in active force in strips of airway smooth muscle (ASM) due to the temporary detachment of bound cross-bridges caused by the relative motion of the actin and myosin fibers. More dramatic and sustained reductions in active force occur following large changes in length. The Huxley two-state model of skeletal muscle originally proposed in 1957 and later adapted to include a four-state description of cross-bridge kinetics has been widely used to model the former phenomenon, but is unable to account for the latter unless modified to include mechanisms by which the contractile machinery in the ASM cell becomes appropriately rearranged. Even so, the Huxley model itself is based on the assumption that the contractile proteins are all aligned precisely in the direction of bulk force generation, which is not true for ASM. The present study derives a coarse-grained version of the Huxley model that is free of inherent assumptions about cross-bridge orientation. This simplified model recapitulates the key features observed in the force-length behavior of activated strips of ASM and, in addition, provides a mechanistically based way of accounting for the sustained force reductions that occur following large stretch.
在气道平滑肌(ASM)条带中,仅施加小百分比的长度变化会导致主动力暂时降低,这是由于肌动蛋白和肌球蛋白纤维的相对运动导致结合的横桥暂时分离所致。长度发生较大变化后,主动力会出现更显著且持续的降低。1957年最初提出的赫胥黎骨骼肌双态模型,后来经过修改纳入了横桥动力学的四态描述,该模型已被广泛用于模拟前一种现象,但除非进行修改以纳入ASM细胞中收缩机制适当重新排列的机制,否则无法解释后一种现象。即便如此,赫胥黎模型本身基于收缩蛋白都精确地沿总力产生方向排列的假设,而这对于ASM来说并不成立。本研究推导了一个粗粒度版本的赫胥黎模型,该模型没有关于横桥方向的固有假设。这个简化模型概括了在激活的ASM条带的力-长度行为中观察到的关键特征,此外,还提供了一种基于机制的方法来解释在大幅拉伸后发生的持续力降低现象。
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