Cardiac Arrhythmias as Manifestations of Nanopathies: An Emerging View.
Cardiac Arrhythmias as Manifestations of Nanopathies: An Emerging View.
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DOI：
10.3389/fphys.2018.01228
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发表时间：
2018
影响因子：
4
通讯作者：
Veeraraghavan R
中科院分区：
文献类型：
--
作者：
Radwański PB;Johnson CN;Györke S;Veeraraghavan R
纳米结构域是位于专门的纳米级结构环境中的蛋白质的集合，可以作为宏观生理过程的功能单元。我们开始认识到心肌细胞纳米结构域在心脏生理学的基本过程中的关键作用，例如电脉冲传播和兴奋收缩耦合（ECC）。人们越来越认识到纳米域功能障碍，即纳米病，是多种病理中危及生命的心律失常的机械驱动因素。在这里，我们概述了纳米域在心脏生理学中的作用的当前研究，特别强调：（1）闰盘内参与细胞间电耦合的富含钠通道的纳米域和（2）位于参与 ECC 的横管上的二元纳米域。心肌细胞的逐搏功能涉及三个阶段：动作电位、钙瞬变和机械收缩/松弛。在所有这些阶段中，细胞范围的功能是单个蛋白质随机功能聚集的结果。虽然人们很早就知道，紧密存在的蛋白质会影响彼此的功能，但人们越来越认识到存在作为心脏生物物理现象的功能单元的纳米级结构。这些结构被称为纳米域，是蛋白质的集合，位于专门的纳米级结构环境中。纳米环境能够产生局部电和/或化学梯度，从而赋予这些单元独特的功能特性。因此，纳米结构域的功能是由其蛋白质成分及其局部结构环境决定的，这为心脏生物学和生物物理学增加了一层额外的复杂性。然而，随着允许在纳米尺度上直接研究结构和功能的实验技术的出现，我们对这些尺度上的心脏生理学和病理生理学的理解正在迅速推进。在这里，我们将讨论多个心肌细胞纳米结构域的结构和功能，以及针对它们治疗心律失常的新策略。
A nanodomain is a collection of proteins localized within a specialized, nanoscale structural environment, which can serve as the functional unit of macroscopic physiologic processes. We are beginning to recognize the key roles of cardiomyocyte nanodomains in essential processes of cardiac physiology such as electrical impulse propagation and excitation–contraction coupling (ECC). There is growing appreciation of nanodomain dysfunction, i.e., nanopathy, as a mechanistic driver of life-threatening arrhythmias in a variety of pathologies. Here, we offer an overview of current research on the role of nanodomains in cardiac physiology with particular emphasis on: (1) sodium channel-rich nanodomains within the intercalated disk that participate in cell-to-cell electrical coupling and (2) dyadic nanodomains located along transverse tubules that participate in ECC. The beat to beat function of cardiomyocytes involves three phases: the action potential, the calcium transient, and mechanical contraction/relaxation. In all these phases, cell-wide function results from the aggregation of the stochastic function of individual proteins. While it has long been known that proteins that exist in close proximity influence each other’s function, it is increasingly appreciated that there exist nanoscale structures that act as functional units of cardiac biophysical phenomena. Termed nanodomains, these structures are collections of proteins, localized within specialized nanoscale structural environments. The nano-environments enable the generation of localized electrical and/or chemical gradients, thereby conferring unique functional properties to these units. Thus, the function of a nanodomain is determined by its protein constituents as well as their local structural environment, adding an additional layer of complexity to cardiac biology and biophysics. However, with the emergence of experimental techniques that allow direct investigation of structure and function at the nanoscale, our understanding of cardiac physiology and pathophysiology at these scales is rapidly advancing. Here, we will discuss the structure and functions of multiple cardiomyocyte nanodomains, and novel strategies that target them for the treatment of cardiac arrhythmias.
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影响因子：
20.1
作者：
Armoundas, AA;Hobai, IA;O'Rourke, B
通讯作者：
O'Rourke, B
影响因子：
1.9
作者：
Copene, Elizabeth D.;Keener, James P.
通讯作者：
Keener, James P.
影响因子：
2.4
作者：
Agullo-Pascual, Esperanza;Delmar, Mario
通讯作者：
Delmar, Mario
影响因子：
5
作者：
Biet, Michael;Barajas-Martinez, Hector;Dumaine, Robert
通讯作者：
Dumaine, Robert
影响因子：
2.4
作者：
Desplantez, Thomas;Dupont, Emmanuel;Weingart, Robert
通讯作者：
Weingart, Robert