Jiang H, Stephens N L
Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Mol Cell Biochem. 1994 Jun 15;135(1):1-9. doi: 10.1007/BF00925956.
The fact that smooth muscle exists in almost every hollow organ and is involved in a large number of disease states has led to a vast increase in smooth muscle research, covering areas from testing response to antagonists and agonists to measuring the molecular force generated by a single actin filament. Yet, the exact mechanisms regulating contractile response of smooth muscle remain unsolved. Calcium has been a central player in mediating smooth muscle contraction through binding with calmodulin, although there is evidence showing that under special circumstances smooth muscle can contract without change in intracellular Ca2+. In addition to the major regulatory pathway of Ca(2+)-calmodulin-myosin light chain kinase, there are other thin filament linked regulatory mechanisms in which Ca(2+)-calmodulin dependent phosphorylation of calponin and caldesmon may be involved. Ca2+ sensitivity of smooth muscle contraction may vary under different situations and this has recently been recognized as an important regulatory mechanism. Examples are protein kinase C (PKC) dependent phosphorylation of myosin light chain kinase which results in partial inhibition of contraction, and activation of myosin light chain phosphatase. There is new evidence showing that not only does Ca2+ regulate contraction by regulating the interaction of contractile proteins in smooth muscle, but also that shortening of smooth muscle itself reduces intracellular Ca2+ concentration, via a negative feedback.
平滑肌几乎存在于每个中空器官中,并与大量疾病状态相关,这一事实导致平滑肌研究大幅增加,涵盖从测试对拮抗剂和激动剂的反应到测量单个肌动蛋白丝产生的分子力等领域。然而,调节平滑肌收缩反应的具体机制仍未解决。钙一直是通过与钙调蛋白结合介导平滑肌收缩的核心因素,尽管有证据表明在特殊情况下平滑肌可以在细胞内Ca2+无变化的情况下收缩。除了Ca(2+)-钙调蛋白-肌球蛋白轻链激酶的主要调节途径外,还有其他细肌丝相关的调节机制,其中钙调蛋白和钙结合蛋白的Ca(2+)-钙调蛋白依赖性磷酸化可能参与其中。平滑肌收缩的Ca2+敏感性在不同情况下可能会有所不同,最近这被认为是一种重要的调节机制。例如,蛋白激酶C(PKC)依赖性的肌球蛋白轻链激酶磷酸化会导致收缩部分受到抑制,以及肌球蛋白轻链磷酸酶的激活。有新证据表明,Ca2+不仅通过调节平滑肌中收缩蛋白的相互作用来调节收缩,而且平滑肌自身的缩短会通过负反馈降低细胞内Ca2+浓度。