Airway smooth muscle, tidal stretches, and dynamically determined contractile states
Airway smooth muscle, tidal stretches, and dynamically determined contractile states
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DOI：
10.1164/ajrccm.156.6.9611016
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发表时间：
1997-12-01
影响因子：
24.7
通讯作者：
Shore, SA
中科院分区：
文献类型：
--
作者：
Fredberg, JJ;Inouye, D;Shore, SA
在哮喘气道管腔狭窄的经典理论中，气道平滑肌中的主动力被假定为与肌肉缩短所对抗的外部负荷处于静态机械平衡。这个理论是有用的，因为它确定了静态平衡长度，如果给予足够的时间，激活的气道平滑肌将趋向于该长度。肌球蛋白-肌动蛋白相互作用趋向的相应状态称为锁存状态。但是，静态机械平衡和闭锁状态的概念是否适用于呼吸期间发生的潮汐负荷的设置？为了解决这个问题，我们已经研究了孤立的，最大限度地收缩牛气管平滑肌在0.33赫兹施加的潮汐拉伸。我们测量了反映肌动蛋白-肌球蛋白相互作用数量的主动力（F）和刚度（E），以及反映这些相互作用转换率的弹性（eta）。当施加的潮气牵张幅值很小时，即肌肉最佳长度的0.25%时，F的稳态值近似于等长力，E较大，eta较小。然而，当E2增加超过1%时，F和E迅速下降，eta迅速增加。只要潮汐拉伸持续，肌肉就可以保持在这些稳定的、动态确定的收缩状态;当收缩率随后降低到0.25%时，F、E和eta缓慢地恢复到它们以前的值。使主动力或肌肉刚度下降一半或使阻力增加一倍所需的刺激性拉伸幅度略大于2%。这些观察结果是一致的桥梁动力学的拉伸后的直接影响，其中，随着潮汐拉伸幅度的增加，肌动蛋白-肌球蛋白相互作用的数量减少，其周转率增加。我们的结论是，肌球蛋白与肌动蛋白的相互作用是在每一个时刻倾向于那些将占上风的等距稳定状态，但肌肉长度的潮汐变化导致过剩的脱离率。与附着速率相比，这些拉伸诱导的脱离事件可能来得如此之快，以至于永远无法达到静态平衡条件。如果是这样的话，那么气道管腔狭窄和潜在的收缩状态将由动态机械过程而不是由静态力的机械平衡来控制。
In the classic theory of airway lumen narrowing in asthma, active force in airway smooth muscle is presumed to be in static mechanical equilibrium with the external load against which the muscle has shortened. This theory is useful because it identifies the static equilibrium length toward which activated airway smooth muscle would tend if given enough time. The corresponding state toward which myosin-actin interactions would tend is called the latch state. But are the concepts of a static mechanical equilibrium and the latch state applicable in the setting of tidal loading, as occurs during breathing? To address this question, we have studied isolated, maximally contracted bovine tracheal smooth muscle subjected to tidal stretches imposed at 0.33 Hz. We measured the active force (F) and stiffness (E), which reflect numbers of actin-myosin interactions, and hysteresivity (eta), which reflects the rate of turnover of those interactions. When the amplitude of imposed tidal stretch (epsilon) was very small, 0.25% of muscle optimal length, the steady-state value of F approximated the isometric force, E was large, and eta was small. When epsilon was increased beyond 1%, however, F and E promptly decreased and eta promptly increased. The muscle could be maintained in these steady, dynamically determined contractile states for as long as the tidal stretches were sustained; when epsilon subsequently decreased back to 0.25%, F, E, and eta returned slowly toward their previous values. The provocative stretch amplitude required to cause active force or muscle stiffness to fall by half, or hysteresivity to double, was slightly greater than 2%. These observations are consistent with a direct effect of stretch upon bridge dynamics in which, with increasing tidal stretch amplitude, the number of actin-myosin interactions decreases and their rate of turnover increases. We conclude that the interactions of myosin with actin are at every instant tending toward those that would prevail in the isometric steady state, but tidal changes of muscle length cause an excess in the rate of detachment. These stretch-induced detachment events can come so fast compared with the rate of attachment that static equilibrium conditions are never attained. If so, then airway lumenal narrowing and the underlying contractile state would be governed by a dynamic mechanical process rather than by a mechanical equilibrium of static forces.