Stephens N L, Fust A, Jiang H, Li W, Ma X
Department of Physiology, University of Manitoba, Winnipeg, Canada.
Can J Physiol Pharmacol. 2005 Oct;83(10):941-51. doi: 10.1139/y05-103.
Smooth muscle relaxation has most often been studied in isometric mode. However, this only tells us about the stiffness properties of the bronchial wall and thus only about wall capacitative properties. It tells us little about airflow. To study the latter, which of course is the meaningful parameter in regulation of ventilation and in asthma, we studied isotonic shortening of bronchial smooth muscle (BSM) strips. Failure of BSM to relax could be another important factor in maintaining high airway resistance. To analyze relaxation curves, we developed an index of isotonic relaxation, t1/2(P, lCE), which is the half-time for relaxation that is independent of muscle load (P) and of initial contractile element length (lCE). This index was measured in curves of relaxation initiated at 2 s (normally cycling crossbridges) and at 10 s (latch-bridges). At 10 s no difference was seen for adjusted t1/2(P, lCE) between curves obtained from control and sensitized BSM, (8.38 +/- 0.92 s vs. 7.78 +/- 0.93 s, respectively). At 2 s the half-time was almost doubled in the sensitized BSM (6.98 +/- 0.01 s (control) vs. 12.74 +/- 2.5 s (sensitized)). Thus, changes in isotonic relaxation are only seen during early contraction. Using zero load clamps, we monitored the time course of velocity during relaxation and noted that it varied according to 3 phases. The first phase (phase i) immediately followed cessation of electrical field stimulation (EFS) at 10 s and showed almost the same velocity as during the latter 1/3 of shortening; the second phase (phase ii) was linear in shape and is associated with zero load velocity, we speculate it could stem from elastic recoil of the cells' internal resistor; and the third phase (phase iii) was convex downwards. The zero load velocities in phase iii showed a surprising spontaneous increase suggesting reactivation of the muscle. Measurements of intracellular calcium (Fura-2 study) and of phosphorylation of the 20 kDa myosin light chain showed simultaneous increments, indicating phase iii represented an active process. Studies are under way to determine what changes occur in these 3 phases in a sensitized muscle. And of course, in the context of this conference, just what role the plastic properties of the muscle play in relaxation requires serious consideration.
平滑肌舒张通常是在等长模式下进行研究的。然而，这仅能告诉我们支气管壁的僵硬特性，进而仅能了解壁的容量特性。它几乎无法告诉我们气流情况。为了研究气流（这当然是通气调节和哮喘中具有重要意义的参数），我们对支气管平滑肌（BSM）条带的等张收缩进行了研究。BSM无法舒张可能是维持高气道阻力的另一个重要因素。为了分析舒张曲线，我们开发了一个等张舒张指数t1/2(P, lCE)，它是与肌肉负荷（P）和初始收缩元件长度（lCE）无关的舒张半衰期。该指数在2秒（正常循环横桥）和10秒（闩锁桥）开始的舒张曲线中进行测量。在10秒时，从对照和致敏BSM获得的曲线之间，调整后的t1/2(P, lCE)没有差异（分别为8.38±0.92秒和7.78±0.93秒）。在2秒时，致敏BSM的半衰期几乎翻倍（对照为6.98±0.01秒，致敏为12.74±2.5秒）。因此，等张舒张的变化仅在早期收缩期间出现。使用零负荷钳，我们监测了舒张过程中速度的时间进程，并注意到它根据三个阶段而变化。第一阶段（阶段i）在10秒电场刺激（EFS）停止后立即出现，其速度与缩短的后1/3期间几乎相同；第二阶段（阶段ii）呈线性，与零负荷速度相关，我们推测它可能源于细胞内电阻器的弹性回缩；第三阶段（阶段iii）向下凸。阶段iii中的零负荷速度显示出惊人的自发增加，表明肌肉重新激活。细胞内钙（Fura-2研究）和20 kDa肌球蛋白轻链磷酸化的测量显示同时增加，表明阶段iii代表一个活跃过程。正在进行研究以确定致敏肌肉在这三个阶段中会发生哪些变化。当然，在本次会议的背景下，肌肉的可塑性特性在舒张中究竟起什么作用需要认真考虑。
