Zhang Wenwu, Gunst Susan J
Dept. of Cellular and Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Dr., Indianapolis, IN 46202-5120, USA.
Proc Am Thorac Soc. 2008 Jan 1;5(1):32-9. doi: 10.1513/pats.200704-048VS.
The ability of airway smooth muscle to alter its stiffness and contractility in response to mechanical oscillation and stretch is critically important for the regulation of normal airway responsiveness during breathing. The properties of mechanical adaptation in airway smooth muscle are proposed to result from dynamic cytoskeletal processes outside of the actomyosin interaction. The actomyosin interaction and crossbridge cycling are viewed as components of a complex and integrated array of cytoskeletal events that occur during cell contraction. These events are orchestrated by macromolecular protein complexes that associate with the cytoplasmic domains of integrin proteins at the adhesion junctions between muscle cells and the extracellular matrix. According to this paradigm, these concerted cytoskeletal events are essential components of the process of active tension generation in airway smooth muscle, and also serve to adapt the shape and stiffness of the smooth muscle cell to its environment. Contractile stimuli initiate actin polymerization within the submembranous cortex of the airway smooth muscle cell that may serve to determine the cells shape and strengthen the membrane. The recruitment of structural proteins such as alpha-actinin to adhesion junctions fortifies the strength of the connections between membrane adhesion junctions and actin filaments. These processes create a strong and rigid cytoskeletal framework for the transmission of force generated by the interaction of myosin and actin filaments. This model for the regulation of airway smooth muscle function can provide novel perspectives to explain the normal physiologic behavior of the airways and pathophysiologic properties of the airways in asthma.
气道平滑肌响应机械振荡和拉伸而改变其硬度和收缩性的能力，对于呼吸过程中正常气道反应性的调节至关重要。气道平滑肌的机械适应性特性被认为是由肌动球蛋白相互作用之外的动态细胞骨架过程导致的。肌动球蛋白相互作用和横桥循环被视为细胞收缩过程中发生的一系列复杂且整合的细胞骨架事件的组成部分。这些事件由大分子蛋白质复合物精心编排，这些复合物在肌肉细胞与细胞外基质之间的黏附连接处与整合素蛋白的细胞质结构域相关联。根据这一范例，这些协同的细胞骨架事件是气道平滑肌主动张力产生过程的重要组成部分，也有助于使平滑肌细胞的形状和硬度适应其环境。收缩刺激引发气道平滑肌细胞膜下皮质内的肌动蛋白聚合，这可能有助于确定细胞形状并强化细胞膜。诸如α - 辅肌动蛋白等结构蛋白募集到黏附连接处，增强了膜黏附连接处与肌动蛋白丝之间连接的强度。这些过程为肌球蛋白和肌动蛋白丝相互作用产生的力的传递创建了一个强大而刚性的细胞骨架框架。这种气道平滑肌功能调节模型可为解释气道的正常生理行为和哮喘中气道的病理生理特性提供新的视角。
