Dynamic equilibration of airway smooth muscle contraction during physiological loading
Dynamic equilibration of airway smooth muscle contraction during physiological loading
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DOI：
10.1152/japplphysiol.01090.2000
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发表时间：
2002-02-01
影响因子：
3.3
通讯作者：
Fredberg, JJ
中科院分区：
文献类型：
--
作者：
Latourelle, J;Fabry, B;Fredberg, JJ
气道平滑肌收缩是哮喘急性气道狭窄的中心事件。大多数对离体肌肉的研究都集中在等长收缩或等张收缩引起的静态平衡收缩状态。然而，最近已经确定，肌肉长度是由肌肉的动态平衡状态决定的，在这种状态下，与呼吸作用相关的小潮汐拉伸会干扰肌球蛋白与肌动蛋白的结合。为了进一步研究这一现象，我们在这份报告中描述了一种实验方法，使离体肌肉受到一个动态的微环境，旨在密切接近体内经历的。与以前的方法，使用随时间变化的长度控制，力控制，或随时间变化的生长负荷，这种方法使用transulpheral压力作为受控变量，肌肉力量和肌肉长度自由调整，因为它们会在体内。该方法是通过使用伺服控制的杠杆臂加载激活的气道平滑肌条与经肺动脉压力波动的幅度增加，模拟呼吸的行动。结果是不一致的气道狭窄，这是一个静态平衡的收缩状态的假设上休息的经典思想，他们是一致的，但是，与肌球蛋白结合的扰动平衡的理论。该实验方法将允许对先前在实验控制之外的因素进行定量实验评价，包括肌肉长度对潮气量变化的敏感性、肺容量变化、负荷特征的形状、实质支持的丧失和气道壁室的炎性增厚。
Airway smooth muscle contraction is the central event in acute airway narrowing in asthma. Most studies of isolated muscle have focused on statically equilibrated contractile states that arise from isometric or isotonic contractions. It has recently been established, however, that muscle length is determined by a dynamically equilibrated state of the muscle in which small tidal stretches associated with the ongoing action of breathing act to perturb the binding of myosin to actin. To further investigate this phenomenon, we describe in this report an experimental method for subjecting isolated muscle to a dynamic microenvironment designed to closely approximate that experienced in vivo. Unlike previous methods that used either time-varying length control, force control, or time-invariant auxotonic loads, this method uses transpulmonary pressure as the controlled variable, with both muscle force and muscle length free to adjust as they would in vivo. The method was implemented by using a servo-controlled lever arm to load activated airway smooth muscle strips with transpulmonary pressure fluctuations of increasing amplitude, simulating the action of breathing. The results are not consistent with classical ideas of airway narrowing, which rest on the assumption of a statically equilibrated contractile state; they are consistent, however, with the theory of perturbed equilibria of myosin binding. This experimental method will allow for quantitative experimental evaluation of factors that were previously outside of experimental control, including sensitivity of muscle length to changes of tidal volume, changes of lung volume, shape of the load characteristic, loss of parenchymal support and inflammatory thickening of airway wall compartments.