Friction in airway smooth muscle: Mechanism, latch, and implications in asthma

Friction in airway smooth muscle: Mechanism, latch, and implications in asthma
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DOI:
10.1152/jappl.1996.81.6.2703
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发表时间:
1996-12-01
影响因子:
3.3
通讯作者:
Sieck, GC
Sieck, GC
中科院分区:
医学2区
文献类型:
--
作者:
Fredberg, JJ;Jones, KA;Sieck, GC

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在肌肉中,主动力量和僵硬反映了肌动蛋白-肌球蛋白相互作用的数量,缩短速度反映了它们的周转率,但机械摩擦的分子基础却不太清楚。为了更好地描述控制机械摩擦的分子机制,我们同时测量了在呼吸过程中受到小周期拉伸的激活犬气道平滑肌的机械能耗散率和肌动球蛋白ATP利用率。摩擦应力的振幅与eta E成正比,其中E是由产生的力与位移回路的斜率定义的组织刚度,而eta是由该回路的脂肪度定义的滞回率。从收缩刺激开始,摩擦应力振幅随肌动球蛋白ATP消耗速率的变化呈双相模式。然而,迟滞性的时间过程遵循与速度缩短不同的双相模式。结合对过桥循环中机械能的储存和耗散的分析,这些结果表明,首先,与缩短速度和肌动球蛋白ATP利用率一样,气道平滑肌的机械摩擦也受过桥循环速率的支配;其次,与快速循环的交叉桥转换为缓慢循环的闩锁桥相关的循环速率变化可以通过力与位移环的迟滞性变化来评估;第三,稳态力维持(闩锁)是一种低摩擦收缩状态。最后一项发现可能解释了哮喘患者无法通过深度吸气逆转自发性气道阻塞的独特原因。
In muscle, active force and stiffness reflect numbers of actin-myosin interactions and shortening velocity reflects their turnover rates, but the molecular basis of mechanical friction is somewhat less clear. To better characterize molecular mechanisms that govern mechanical friction, we measured the rate of mechanical energy dissipation and the rate of actomyosin ATP utilization simultaneously in activated canine airway smooth muscle subjected to small periodic stretches as occur in breathing. The amplitude of the frictional stress is proportional to eta E, where E is the tissue stiffness defined by the slope of the resulting force vs. displacement loop and eta is the hysteresivity defined by the fatness of that loop. From contractile stimulus onset, the time course of frictional stress amplitude followed a biphasic pattern that tracked that of the rate of actomyosin ATP consumption. The time course of hysteresivity, however, followed a different biphasic pattern that tracked that of shortening velocity. Taken together with an analysis of mechanical energy storage and dissipation in the cross-bridge cycle, these results indicate, first, that like shortening velocity and the rate of actomyosin ATP utilization, mechanical friction in airway smooth muscle is also governed by the rate of cross-bridge cycling; second, that changes in cycling rate associated with conversion of rapidly cycling cross bridges to slowly cycling latch bridges can be assessed from changes of hysteresivity of the force vs. displacement loop; and third, that steady-state force maintenance (latch) is a low-friction contractile state. This last finding may account for the unique inability of asthmatic patients to reverse spontaneous airways obstruction with a deep inspiration.