Calaghan S C, Le Guennec J-Y, White E
School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK.
Prog Biophys Mol Biol. 2004 Jan;84(1):29-59. doi: 10.1016/s0079-6107(03)00057-9.
The cardiac myocyte has an intracellular scaffold, the cytoskeleton, which has been implicated in several cardiac pathologies including hypertrophy and failure. In this review we describe the role that the cytoskeleton plays in modulating both the electrical activity (through ion channels and exchangers) and mechanical (or contractile) activity of the adult heart. We focus on the 3 components of the cytoskeleton, actin microfilaments, microtubules, and desmin filaments. The limited visual data available suggest that the subsarcolemmal actin cytoskeleton is sparse in the adult myocyte. Selective disruption of cytoskeletal actin by pharmacological tools has yet to be verified in the adult cell, yet evidence exists for modulation of several ionic currents, including I(CaL), I(Na), I(KATP), I(SAC) by actin microfilaments. Microtubules exist as a dense network throughout the adult cardiac cell, and their structure, architecture, kinetics and pharmacological manipulation are well described. Both polymerised and free tubulin are functionally significant. Microtubule proliferation reduces contraction by impeding sarcomeric motion; modulation of sarcoplasmic reticulum Ca(2+) release may also be involved in this effect. The lack of effect of microtubule disruption on cardiac contractility in adult myocytes, and the concentration-dependent modulation of the rate of contraction by the disruptor nocodazole in neonatal myocytes, support the existence of functionally distinct microtubule populations. We address the controversy regarding the stimulation of the beta-adrenergic signalling pathway by free tubulin. Work with mice lacking desmin has demonstrated the importance of intermediate filaments to normal cardiac function, but the precise role that desmin plays in the electrical and mechanical activity of cardiac muscle has yet to be determined.
心肌细胞具有细胞内支架，即细胞骨架，它与包括肥大和衰竭在内的多种心脏疾病有关。在这篇综述中，我们描述了细胞骨架在调节成年心脏的电活动（通过离子通道和交换体）和机械（或收缩）活动中所起的作用。我们重点关注细胞骨架的三个组成部分：肌动蛋白微丝、微管和结蛋白丝。现有的有限视觉数据表明，成年心肌细胞中肌膜下的肌动蛋白细胞骨架稀疏。在成年细胞中，通过药理学工具对细胞骨架肌动蛋白进行选择性破坏尚未得到证实，但有证据表明肌动蛋白微丝可调节多种离子电流，包括L型钙电流（I(CaL)）、钠电流（I(Na)）、ATP敏感性钾电流（I(KATP)）、慢失活钾电流（I(SAC)）。微管在整个成年心脏细胞中以密集网络的形式存在，其结构、架构、动力学和药理学操作都有详细描述。聚合的和游离的微管蛋白在功能上都很重要。微管增殖通过阻碍肌节运动来减少收缩；肌浆网钙释放的调节可能也参与了这种作用。微管破坏对成年心肌细胞心脏收缩力没有影响，而破坏剂诺考达唑对新生心肌细胞收缩速率的浓度依赖性调节，支持了功能上不同的微管群体的存在。我们讨论了关于游离微管蛋白对β-肾上腺素能信号通路刺激的争议。对缺乏结蛋白的小鼠的研究表明，中间丝对正常心脏功能很重要，但结蛋白在心肌电活动和机械活动中的确切作用尚未确定。
