Ankyrin-G participates in INa remodeling in myocytes from the border zones of infarcted canine heart.
Ankyrin-G participates in INa remodeling in myocytes from the border zones of infarcted canine heart.
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DOI：
10.1371/journal.pone.0078087
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Boyden PA
中科院分区：
文献类型：
--
作者：
Dun W;Lowe JS;Wright P;Hund TJ;Mohler PJ;Boyden PA
心脏钠通道重构为梗死犬心脏边缘区折返性心律失常的发生提供了重要的基础。最近的研究表明，Nav1.5的组装和功能与锚蛋白-G，间隙和机械连接蛋白有关。在这项研究中，我们的目的是阐述心肌钠通道，其相互作用的蛋白质ankrexG和机械和间隙连接蛋白在两个不同的时间梗死后心律失常时，发生的状态，即48小时和5天后冠状动脉闭塞。以往的研究表明，心脏事件的起源来自心内膜下浦肯野和心外膜边缘区。我们的浦肯野细胞（Pcell）电压钳研究表明，梗死48小时心肌内膜下Pcell（IZPC）和对照非梗死Pcell（NZPC）的INa及其动力学参数没有差异。免疫染色研究显示，在48小时IZPC中，Nav1.5蛋白定位与ankrex-G的干扰是适度的。因此，钠电流重构并不有助于异常传导的内膜下边缘区心肌梗死后48小时，如前所述。此外，免疫组化数据显示，Cx40/Cx43共定位于对照NZPC的闰盘（ID），但在IZPC中分离。同时，浦肯野细胞桥粒斑蛋白和桥粒核心蛋白2免疫染色变得弥漫，而斑嗜蛋白2和斑珠蛋白在ID时丰度增加。在心肌梗死后5天的心外膜边缘区，免疫印迹和免疫细胞化学分析显示，在Nav1.5功能降低时，ankrex-G蛋白表达增加并重新定位于膜下细胞区域。因此，Nav1.5和锚定-G重塑发生后心肌梗死相比，间隙和机械连接蛋白。间隙和机械连接蛋白在IZPC早期重塑，可能有助于维持Nav1.5亚细胞定位位置并在心肌梗死后不久保持其功能。
Cardiac Na channel remodeling provides a critical substrate for generation of reentrant arrhythmias in border zones of the infarcted canine heart. Recent studies show that Nav1.5 assembly and function are linked to ankyrin-G, gap, and mechanical junction proteins. In this study our objective is to expound the status of the cardiac Na channel, its interacting protein ankyrinG and the mechanical and gap junction proteins at two different times post infarction when arrhythmias are known to occur; that is, 48 hr and 5 day post coronary occlusion. Previous studies have shown the origins of arrhythmic events come from the subendocardial Purkinje and epicardial border zone. Our Purkinje cell (Pcell) voltage clamp study shows that INa and its kinetic parameters do not differ between Pcells from the subendocardium of the 48hr infarcted heart (IZPCs) and control non-infarcted Pcells (NZPCs). Immunostaining studies revealed that disturbances of Nav1.5 protein location with ankyrin-G are modest in 48 hr IZPCs. Therefore, Na current remodeling does not contribute to the abnormal conduction in the subendocardial border zone 48 hr post myocardial infarction as previously defined. In addition, immunohistochemical data show that Cx40/Cx43 co-localize at the intercalated disc (IDs) of control NZPCs but separate in IZPCs. At the same time, Purkinje cell desmoplakin and desmoglein2 immunostaining become diffuse while plakophilin2 and plakoglobin increase in abundance at IDs. In the epicardial border zone 5 days post myocardial infarction, immunoblot and immunocytochemical analyses showed that ankyrin-G protein expression is increased and re-localized to submembrane cell regions at a time when Nav1.5 function is decreased. Thus, Nav1.5 and ankyrin-G remodeling occur later after myocardial infarction compared to that of gap and mechanical junctional proteins. Gap and mechanical junctional proteins remodel in IZPCs early, perhaps to help maintain Nav1.5 subcellular location position and preserve its function soon after myocardial infarction.
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影响因子：
37.8
作者：
Koval OM;Snyder JS;Wolf RM;Pavlovicz RE;Glynn P;Curran J;Leymaster ND;Dun W;Wright PJ;Cardona N;Qian L;Mitchell CC;Boyden PA;Binkley PF;Li C;Anderson ME;Mohler PJ;Hund TJ
通讯作者：
Hund TJ
DOI：
10.1073/pnas.0403711101
发表时间：
2004-12-14
影响因子：
11.1
作者：
Mohler, PJ;Rivolta, I;Bennett, V
通讯作者：
Bennett, V
影响因子：
37.8
作者：
Baba, S;Dun, W;Boyden, PA
通讯作者：
Boyden, PA
影响因子：
4.8
作者：
Abdi, KM;Mohler, PJ;Bennett, V
通讯作者：
Bennett, V
影响因子：
6.6
作者：
Pieperhoff, Sebastian;Borrmann, Carola;Franke, Werner W.
通讯作者：
Franke, Werner W.