Kaprielian R R, Severs N J
National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
Heart Fail Rev. 2000 Oct;5(3):221-38. doi: 10.1023/A:1009805419285.
The cardiomyocyte membrane cytoskeleton consists of the costameric proteins that mediate force transduction from the cell to the extracellular matrix, and a sub-membrane network composed of dystrophin and associated proteins. Studies of the precise cellular distribution of dystrophin and of the consequences of genetic mutations leading to abnormal expression of the dystrophin molecule, as occurs in Duchenne and Becker's muscular dystrophies, highlight potential functional roles of this sub-membrane protein complex in cardiomyocytes. Detailed investigation of dystrophin distribution using the complementary cell imaging techniques of immunoconfocal microscopy and freeze-fracture cytochemistry at the electron-microscopical level show that, in contrast to rat cardiomyocytes, the dystrophin network in human cardiomyocytes is locally enriched at costameres. Thus located, the dystrophin network appears to have a mechanical role, involving stabilization of the peripheral plasma membrane during the repetitive distortion associated with cardiac contraction and, in the human myocyte, contributing to lateral force-transduction. Evidence from animal models of muscular dystrophy and from investigation of the interactions of the sub-membrane cytoskeleton with other membrane-associated proteins including ion channels, receptors and enzymes, further suggests a role for dystrophin in organization and regulation of membrane domains. The relative preservation of the membrane cytoskeleton in non-dystrophic dilated cardiomyopathy and in ischemic cardiomyopathy, conditions in which the myocyte contractile apparatus and internal desmin-based cytoskeleton are commonly disrupted, emphasizes the vital role of the membrane cytoskeleton in cell survival. Continued cardiomyocyte survival despite loss of contractile protein organization has implications in the potential for reversibility of left ventricular remodeling that can be achieved in the clinical setting.
心肌细胞膜细胞骨架由介导从细胞到细胞外基质的力传导的肌联蛋白组成，以及由肌营养不良蛋白和相关蛋白组成的膜下网络。对肌营养不良蛋白精确细胞分布的研究，以及对导致肌营养不良蛋白分子异常表达的基因突变后果的研究（如在杜兴氏和贝克氏肌营养不良症中发生的那样），突出了这种膜下蛋白复合物在心肌细胞中的潜在功能作用。在电子显微镜水平上，使用免疫共聚焦显微镜和冷冻断裂细胞化学等互补细胞成像技术对肌营养不良蛋白分布进行的详细研究表明，与大鼠心肌细胞不同，人类心肌细胞中的肌营养不良蛋白网络在肌节处局部富集。位于此处的肌营养不良蛋白网络似乎具有机械作用，包括在与心脏收缩相关的重复变形过程中稳定外周质膜，并且在人类心肌细胞中有助于侧向力传导。来自肌营养不良动物模型的证据以及对膜下细胞骨架与其他膜相关蛋白（包括离子通道、受体和酶）相互作用的研究，进一步表明肌营养不良蛋白在膜结构域的组织和调节中起作用。在非营养不良性扩张型心肌病和缺血性心肌病中，肌细胞膜细胞骨架相对保留，而在这些疾病中，心肌细胞收缩装置和基于结蛋白的内部细胞骨架通常会被破坏，这强调了膜细胞骨架在细胞存活中的重要作用。尽管收缩蛋白组织丧失，但心肌细胞仍能存活，这对临床环境中可实现的左心室重塑的可逆性潜力具有重要意义。
