Sodium channel clusters: harmonizing the cardiac conduction orchestra.
Sodium channel clusters: harmonizing the cardiac conduction orchestra.
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钠通道簇：协调心脏传导管弦乐队。
DOI：
10.1113/jp275632
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Radwański,PrzemysławB
中科院分区：
文献类型：
--
作者：
Veeraraghavan,Rengasayee;Radwański,PrzemysławB
现在人们广泛认识到，生物系统中的蛋白质被组织成大分子复合物，并且这种组织是其功能的关键决定因素。这在很大程度上是由于从分子生物学研究中获得的见解。我们现在正在进入另一个变革时期，因为新兴技术，如超分辨率显微镜，揭示了纳米级蛋白质的组织及其局部结构环境。这些新的结构见解要求从根本上重新审视蛋白质在这些尺度上如何产生组织和器官水平的功能。这种范式转变的影响在心脏生物物理学等领域最为明显。事实上，许多离子通道以簇的形式存在，与结构和调节蛋白非常接近，并且通常被限制性的细胞内/细胞外裂隙包围，这一认识正在改变我们对心脏电生理学和兴奋-收缩耦合的理解。
It is now widely appreciated that proteins within biological systems are organized into macromolecular complexes and that such organization is a key determinant of their function. This is due, in large part, to insights gained from molecular biology studies. We are now entering another transformative period as emerging techniques such as super-resolution microscopy shed light on the organization of proteins at the nanoscale and their local structural environment. These new structural insights invite a fundamental re-examination of how proteins behave at these scales to produce tissue and organ level function. The impact of this paradigm shift is most evident in fields such as cardiac biophysics. Indeed, the understanding that many ion channels exist in clusters, in close proximity to structural and regulatory proteins, and often surrounded by restricted intra-/extracellular clefts is transforming our understanding of cardiac electrophysiology and excitation–contraction coupling.