Structure-function relationship in the AV junction
Structure-function relationship in the AV junction
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DOI：
10.1002/ar.a.20108
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发表时间：
2004-10-01
期刊：
影响因子：
--
通讯作者：
Boyett, M
中科院分区：
文献类型：
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作者：
Efimov, IR;Nikolski, VP;Boyett, M
在正常心脏中，房室结（AVN）是心房和心室之间唯一通路的一部分。在正常生理条件下，AVN 控制适当的频率依赖性收缩延迟。 AVN 在病理学中也发挥着重要作用：它在房性快速心律失常期间保护心室，在窦房结衰竭期间，AV 连接起搏器可以驱动心脏。最后，房室连接处为折返提供解剖学基质。使用电压敏感染料荧光成像和免疫组织化学，我们研究了房室结在正常传导、折返和交界节律期间的结构-功能关系。我们确定了分子和结构异质性，为双通路 AVN 传导提供了底物。我们观察到三种连接蛋白亚型的表达异质性：Cx43、Cx45 和 Cx40。我们在 79% (n = 14) 的研究心脏中确定了交界节律的起源部位位于房室结后部延伸处。通过形态学和分子研究确定，这种结构类似于紧凑的房室结。特别是，后延伸和致密结都表达起搏通道 HCN4（负责 1，电流）和神经丝 160。在兔心脏中，房室结传导、折返性心律失常和自发节律受间隙连接和离子通道的几种亚型表达的异质性控制。均匀的神经丝表达表明房室结后部延伸是心脏起搏和传导系统的组成部分。另一方面，该区域 Cx 亚型的差异表达为纵向解离、双通路电生理学和房室结折返性心律失常发生提供了解释。 (C) 2004 Wiley-Liss, Inc.
In the normal heart, the atrioventricular node (AVN) is part of the sole pathway between the atria and ventricles. Under normal physiological conditions, the AVN controls appropriate frequency-dependent delay of contractions. The AVN also plays an important role in pathology: it protects ventricles during atrial tachyarrhythmia, and during sinoatrial node failure an AV junctional pacemaker can drive the heart. Finally, the AV junction provides an anatomical substrate for reentry. Using fluorescent imaging with voltage-sensitive dyes and immunohistochemistry, we have investigated the structure-function relationship of the AV junction during normal conduction, reentry, and junctional rhythm. We identified molecular and structural heterogeneity that provides a substrate for the dual-pathway AVN conduction. We observed heterogeneity of expression of three isoforms of connexins: Cx43, Cx45, and Cx40. We identified the site of origin of junctional rhythm at the posterior extension of the AV node in 79% (n = 14) of the studied hearts. This structure was similar to the compact AV node as determined by morphologic and molecular investigations. In particular, both the posterior extension and the compact node express the pacemaking channel HCN4 (responsible for the 1, current) and neurofilament 160. In the rabbit heart, AV junction conduction, reentrant arrhythmia, and spontaneous rhythm are governed by heterogeneity of expression of several isoforms of gap junctions and ion channels. Uniform neurofilament expression suggests that AV nodal posterior extensions are an integral part of the cardiac pacemaking and conduction system. On the other hand, differential expression of Cx isoforms in this region provides an explanation of longitudinal dissociation, dual-pathway electrophysiology, and AV nodal reentrant arrhythmogenesis. (C) 2004 Wiley-Liss, Inc.