James Hogg iCAPTURE Centre/St. Paul's Hospital, 1081 Burrard St., Vancouver, BC, Canada.
Am J Physiol Lung Cell Mol Physiol. 2010 Mar;298(3):L277-87. doi: 10.1152/ajplung.00275.2009. Epub 2009 Dec 11.
The amplitude of strain in airway smooth muscle (ASM) produced by oscillatory perturbations such as tidal breathing or deep inspiration (DI) influences the force loss in the muscle and is therefore a key determinant of the bronchoprotective and bronchodilatory effects of these breathing maneuvers. The stiffness of unstimulated ASM (passive stiffness) directly influences the amplitude of strain. The nature of the passive stiffness is, however, not clear. In this study, we measured the passive stiffness of ovine ASM at different muscle lengths (relative to in situ length, which was used as a reference length, L(ref)) and states of adaptation to gain insights into the origin of this muscle property. The results showed that the passive stiffness was relatively independent of muscle length, possessing a constant plateau value over a length range from 0.62 to 1.25 L(ref). Following a halving of ASM length, passive stiffness decreased substantially (by 71%) but redeveloped over time ( approximately 30 min) at the shorter length to reach 65% of the stiffness value at L(ref), provided that the muscle was stimulated to contract at least once over a approximately 30-min period. The redevelopment and maintenance of passive stiffness were dependent on the presence of Ca(2+) but unaffected by latrunculin B, an inhibitor of actin filament polymerization. The maintenance of passive stiffness was also not affected by blocking myosin cross-bridge cycling using a myosin light chain kinase inhibitor or by blocking the Rho-Rho kinase (RhoK) pathway using a RhoK inhibitor. Our results suggest that the passive stiffness of ASM is labile and capable of redevelopment following length reduction. Redevelopment and maintenance of passive stiffness following muscle shortening could contribute to airway hyperresponsiveness by attenuating the airway wall strain induced by tidal breathing and DI.
气道平滑肌（ASM）在振荡扰动（如潮汐呼吸或深呼吸（DI））下产生的应变幅度影响肌肉的力损失，因此是这些呼吸动作的支气管保护和支气管扩张作用的关键决定因素。未受刺激的 ASM 的刚性（被动刚度）直接影响应变幅度。然而，被动刚度的性质尚不清楚。在这项研究中，我们测量了不同肌肉长度（相对于原位长度，用作参考长度，L(ref)）和适应状态下的绵羊 ASM 的被动刚度，以深入了解这种肌肉特性的起源。结果表明，被动刚度相对独立于肌肉长度，在 0.62 至 1.25 L(ref)的长度范围内具有恒定的平台值。ASM 长度减半后，被动刚度显着下降（下降 71%），但在较短的长度下会随着时间的推移（约 30 分钟）重新发展，达到 L(ref)处刚度值的 65%，前提是肌肉在大约 30 分钟的时间内至少受到一次刺激以收缩。被动刚度的重新发展和维持取决于 Ca(2+)的存在，但不受肌动蛋白丝聚合抑制剂 latrunculin B 的影响。使用肌球蛋白轻链激酶抑制剂阻断肌球蛋白交联循环或使用 RhoK 抑制剂阻断 Rho-Rho 激酶（RhoK）途径对被动刚度的维持没有影响。我们的结果表明，ASM 的被动刚度不稳定，并且在长度减小后能够重新发展。缩短肌肉后被动刚度的重新发展和维持可能通过减轻潮汐呼吸和 DI 引起的气道壁应变来导致气道高反应性。
