Institute of Biomedical Technologies, Auckland University of Technology, Auckland, New Zealand.
J Appl Physiol (1985). 2011 Sep;111(3):735-42. doi: 10.1152/japplphysiol.00114.2011. Epub 2011 Jun 9.
Length adaptation in airway smooth muscle (ASM) is attributed to reorganization of the cytoskeleton, and in particular the contractile elements. However, a constantly changing lung volume with tidal breathing (hence changing ASM length) is likely to restrict full adaptation of ASM for force generation. There is likely to be continuous length adaptation of ASM between states of incomplete or partial length adaption. We propose a new model that assimilates findings on myosin filament polymerization/depolymerization, partial length adaptation, isometric force, and shortening velocity to describe this continuous length adaptation process. In this model, the ASM adapts to an optimal force-generating capacity in a repeating cycle of events. Initially the myosin filament, shortened by prior length changes, associates with two longer actin filaments. The actin filaments are located adjacent to the myosin filaments, such that all myosin heads overlap with actin to permit maximal cross-bridge cycling. Since in this model the actin filaments are usually longer than myosin filaments, the excess length of the actin filament is located randomly with respect to the myosin filament. Once activated, the myosin filament elongates by polymerization along the actin filaments, with the growth limited by the overlap of the actin filaments. During relaxation, the myosin filaments dissociate from the actin filaments, and then the cycle repeats. This process causes a gradual adaptation of force and instantaneous adaptation of shortening velocity. Good agreement is found between model simulations and the experimental data depicting the relationship between force development, myosin filament density, or shortening velocity and length.
气道平滑肌（ASM）的长度适应归因于细胞骨架的重组，特别是收缩元件。然而，潮气量呼吸引起的不断变化的肺容积（因此改变 ASM 长度）可能会限制 ASM 产生力的完全适应。在不完全或部分长度适应的状态之间，ASM 可能会持续进行长度适应。我们提出了一个新的模型，该模型将肌球蛋白丝聚合/解聚、部分长度适应、等长力和缩短速度的发现结合起来，以描述这种连续的长度适应过程。在这个模型中，ASM 在一个重复的事件循环中适应最佳的力产生能力。最初，由先前的长度变化缩短的肌球蛋白丝与两个较长的肌动蛋白丝结合。肌动蛋白丝位于肌球蛋白丝的旁边，使得所有的肌球蛋白头部与肌动蛋白重叠，以允许最大的横桥循环。由于在这个模型中，肌动蛋白丝通常比肌球蛋白丝长，所以肌动蛋白丝的多余长度相对于肌球蛋白丝是随机定位的。一旦被激活，肌球蛋白丝通过沿肌动蛋白丝聚合而伸长，生长受到肌动蛋白丝重叠的限制。在松弛过程中，肌球蛋白丝从肌动蛋白丝上解离，然后循环重复。这个过程导致力的逐渐适应和缩短速度的瞬间适应。模型模拟与描述力发展、肌球蛋白丝密度或缩短速度与长度之间关系的实验数据之间存在很好的一致性。
