Length adaptation of airway smooth muscle.
Length adaptation of airway smooth muscle.
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DOI：
10.1513/pats.200705-056vs
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发表时间：
2008-01-01
期刊：
影响因子：
--
通讯作者：
Seow, Chun Y
中科院分区：
文献类型：
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作者：
Bosse, Ynuk;Sobieszek, Apolinary;Seow, Chun Y
许多类型的平滑肌，包括气道平滑肌（ASM），由于长度适应，能够在大长度范围内产生最大的力，这是一个相对快速的过程，平滑肌在经历长度波动引起的力减少后恢复收缩力。尽管潜在的机制尚不清楚，但人们认为平滑肌细胞的结构延展性是适应发生的必要条件。这一过程是由细胞骨架上的应变触发的，导致一系列尚未定义的生化和生物物理事件，导致细胞骨架和收缩装置的重组，从而优化肌凝蛋白和肌动蛋白丝之间的重叠。虽然长度适应性是平滑肌的固有特性，但ASM的不适应可能导致气道过度收缩和深吸气无法扩张。在这篇文章中，我们描述了肌凝蛋白的长度适应现象和一些可能的潜在机制，包括肌凝蛋白丝的组装和拆卸。我们讨论了ASM的不适应在哮喘发病机制中的可能作用。我们认为，ASM中的长度适应是由特定蛋白及其翻译后调控介导的，包括共价修饰，如磷酸化。这些分子及其活动调控过程的发现将极大地增强我们对ASM收缩基本机制的理解，并将提出缓解与气道过度收缩相关的哮喘加重的分子靶点。
Many types of smooth muscle, including airway smooth muscle (ASM), are capable of generating maximal force over a large length range due to length adaptation, which is a relatively rapid process in which smooth muscle regains contractility after experiencing a force decrease induced by length fluctuation. Although the underlying mechanism is unclear, it is believed that structural malleability of smooth muscle cells is essential for the adaptation to occur. The process is triggered by strain on the cell cytoskeleton that results in a series of yet undefined biochemical and biophysical events leading to restructuring of the cytoskeleton and contractile apparatus and consequently optimization of the overlap between the myosin and actin filaments. Although length adaptability is an intrinsic property of smooth muscle, maladaptation of ASM could result in excessive constriction of the airways and the inability of deep inspirations to dilate them. In this article, we describe the phenomenon of length adaptation in ASM and some possible underlying mechanisms that involve the myosin filament assembly and disassembly. We discuss a possible role of maladaptation of ASM in the pathogenesis of asthma. We believe that length adaptation in ASM is mediated by specific proteins and their posttranslational regulations involving covalent modifications, such as phosphorylation. The discovery of these molecules and the processes that regulate their activity will greatly enhance our understanding of the basic mechanisms of ASM contraction and will suggest molecular targets to alleviate asthma exacerbation related to excessive constriction of the airways.