Ion channel macromolecular complexes in cardiomyocytes: roles in sudden cardiac death.
Ion channel macromolecular complexes in cardiomyocytes: roles in sudden cardiac death.
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DOI：
10.1161/circresaha.116.305017
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发表时间：
2015-06-05
影响因子：
20.1
通讯作者：
Jalife J
中科院分区：
文献类型：
--
作者：
Abriel H;Rougier JS;Jalife J
离子穿过嵌入在单个心肌细胞膜上的特定通道的运动对于心脏电脉冲的产生和传播是至关重要的。在过去的20年中出现的证据强烈表明，心脏的正常电功能是膜离子通道的动态相互作用的结果，这些离子通道作为复杂分子网络的一部分以协调的方式工作。这些网络以精确的时间精度协同工作，产生每一个动作电位和收缩。大分子复合物在迄今已知的所有心脏离子通道的转录、翻译、寡聚化、运输、膜保留、糖基化、翻译后修饰、周转、功能和降解中起着至关重要的作用。此外，每次心跳和收缩的准确定时要求在特定亚细胞微域内钠、钙和钾通道复合物的组装和组织上具有相当的精度，其中物理接近允许迅速和有效的相互作用。这篇综述文章，心脏性猝死纲要的一部分，讨论了离子通道大分子组装体在正常心脏电功能中的作用以及心律失常导致心脏性猝死的机制。它提供了一个想法，这些问题是如何在实验室和临床上解决的，哪些重要的问题仍然没有答案，以及未来需要什么样的研究来提高知识和推进治疗。
The movement of ions across specific channels embedded on the membrane of individual cardiomyocytes is crucial for the generation and propagation of the cardiac electrical impulse. Emerging evidence over the last 20 years strongly suggests that the normal electrical function of the heart is the result of dynamic interactions of membrane ion channels working in an orchestrated fashion as part of complex molecular networks. Such networks work together with exquisite temporal precision to generate each action potential and contraction. Macromolecular complexes play crucial roles in transcription, translation, oligomerization, trafficking, membrane retention, glycosylation, posttranslational modification, turnover, function and degradation of all cardiac ion channels known to date. In addition, the accurate timing of each cardiac beat and contraction demands, a comparable precision on the assembly and organizations of sodium, calcium and potassium channel complexes within specific subcellular microdomains, where physical proximity allows for prompt and efficient interaction. This review article, part of the Compendium on Sudden Cardiac Death, discusses the major issues related to the role of ion channel macromolecular assemblies in normal cardiac electrical function and the mechanisms of arrhythmias leading to sudden cardiac death. It provides an idea of how these issues are being addressed in the laboratory and in the clinic, which important questions remain unanswered, and what future research will be needed to improve knowledge and advance therapy.