The molecular mechanisms of gap junction remodeling.
The molecular mechanisms of gap junction remodeling.
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DOI：
10.1016/j.hrthm.2011.11.048
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发表时间：
2012-08
期刊：
影响因子：
5.5
通讯作者：
Duffy, Heather S.
中科院分区：
文献类型：
--
作者：
Duffy, Heather S.
1967年，Revel和Karnovsky首次描述了一种膜相关颗粒的聚集体，虽然看起来它们阻塞了细胞外空间，但允许示踪剂氢氧化镧通过聚集体之间的小间隙，并将这种颗粒簇命名为“间隙连接”[1]。在心脏中，他们将这些结构描述为主要位于细胞的长端，称为闰盘（ID）。Page及其同事的进一步研究注意到在差距连接下存在“模糊涂层”，从而引起了细胞外聚集体穿过肌细胞膜并锚定在细胞内的推测[2]。从这些早期的研究中产生了一个新的研究领域，即这些聚集体是由什么组成的以及它们如何工作。在心脏研究中，心脏间隙连接的主要成分被鉴定为43 kD蛋白[3]，随后被命名为连接蛋白43（Cx43）。研究表明，与肝细胞不同，肝细胞连接蛋白Connexin 32位于整个细胞中[4]，在心脏的肌细胞中，连接蛋白优先位于闰盘处的细胞末端，因此显示肌细胞纵切面的图像显示肌细胞末端明显的染色直线（图1A）。横向图像显示，Cx43并没有覆盖整个肌细胞末端，而是位于闰盘边缘周围的环中（图1B）。这种模式已在小鼠[5]、犬[6]和人类心脏[7]中显示，表明这种高度组织化的模式在物种间是保守的。对缝隙连接作为电流通道功能的理解导致了心脏中Cx43的定位对于心脏的正常各向异性传导是重要的假设。当Cx43染色的患病心脏图像显示心脏病理与心室肌中Cx43的正常模式的改变有关时，引起了对缝隙连接在心脏疾病中的作用的兴趣。7]。心肌梗死后人类心脏中的Cx43不是位于闰盘，而是位于肌细胞的侧面，称为侧膜。由于Cx43的闰盘定位被认为对正常心脏的各向异性传导是重要的，因此Cx43的这种“偏侧化”被怀疑与损伤心脏的传导改变有关。随后的研究表明，Cx43的这种结构重塑在脑组织中可能是一种重要的机制。
In 1967, Revel and Karnovsky first described an aggregate of membrane associated particles which, while looking like they blocked the extracellular space, allowed the tracer Lanthanum Hydroxyde, to pass through small gaps between the aggregates, and gave this cluster of particles the name “gap junction”[1]. In the heart, they described these structures to be primarily at the long ends of the cells, identified as the intercalated disk (ID). Further studies by Page and his colleagues noted the presence of a “fuzzy coat” under the gap junctions, giving rise to the speculation that the extracellular aggregates crossed the myocyte membrane and anchored within the cell [2]. From these early studies grew a new field of research into what these aggregates were made of and how they worked. In cardiac studies, the primary component of cardiac gap junctions was identified as a 43 kD protein [3] subsequently named Connexin43 (Cx43). Studies showed that unlike the liver cells, where the hepatocyte connexin, Connexin32, was localized all over the cells [4], in the myocytes of the heart, connexins were preferential localized to the ends of cells at the intercalated disks such that images showing longitudinal sections of myocytes gave a straight line of staining that was evident at myocyte ends (Figure 1A). Transverse images show that the Cx43 does not cover the entire ends of the myocytes, rather it is positioned in a ring around the edges of the intercalated disk (Figure 1B). This pattern has been shown in mouse [5], dog [6] and human heart [7] indicating that this highly organized pattern is conserved across species. Understanding of the function of gap junctions as conduits for electrical current led to hypotheses that the localization of Cx43 in heart was important for the normal anisotropic conduction of the heart.Interest in the role of gap junctions in heart disease was piqued when images of diseased hearts stained for Cx43 showed that cardiac pathologies were associated with a change in the normal pattern of Cx43 in the ventricular myocardium [7]. Rather than being localized at the intercalated disk, Cx43 in human hearts after a myocardial infarction was found on the sides of the myocytes, known as the lateral membranes. Being as intercalated disk localization of Cx43 was considered important for anisotropic conduction in normal heart, this “lateralization” of Cx43 was suspected to be involved in alterations of conduction in the injured heart. Subsequent studies have shown that this structural remodeling of Cx43 in the
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在愈合犬梗死的心外膜边界区域的间隙连接重塑的表征以及Rotigaptide部分逆转的电生理效应。
DOI：
10.1161/circep.110.959312
发表时间：
2011-06
期刊：
Circulation. Arrhythmia and electrophysiology
影响因子：
--
作者：
Macia E;Dolmatova E;Cabo C;Sosinsky AZ;Dun W;Coromilas J;Ciaccio EJ;Boyden PA;Wit AL;Duffy HS
通讯作者：
Duffy HS
DOI：
10.1042/bj20082319
发表时间：
2009-04-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Solan JL;Lampe PD
通讯作者：
Lampe PD
影响因子：
20.1
作者：
Duffy, HS;Ashton, AW;Spray, DC
通讯作者：
Spray, DC
影响因子：
20.1
作者：
Gutstein, DE;Morley, GE;Fishman, GI
通讯作者：
Fishman, GI
影响因子：
7.8
作者：
GOODENOUGH, DA;PAUL, DL;JESAITIS, L
通讯作者：
JESAITIS, L