Connexin40 imparts conduction heterogeneity to atrial tissue.
Connexin40 imparts conduction heterogeneity to atrial tissue.
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DOI：
10.1161/circresaha.107.168997
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发表时间：
2008-10-24
影响因子：
20.1
通讯作者：
Morley GE
中科院分区：
文献类型：
--
作者：
Leaf DE;Feig JE;Vasquez C;Riva PL;Yu C;Lader JM;Kontogeorgis A;Baron EL;Peters NS;Fisher EA;Gutstein DE;Morley GE
脉冲在心脏组织中的传播是一个复杂的过程，其中通过间隙连接通道的细胞间耦合是一个关键组成部分。缝隙连接蛋白40（Cx40）是一种在心房肌细胞中大量表达的缝隙连接蛋白。Cx40表达的改变与心房肌纤维化有关。本研究的目的是评估Cx40在心房冲动传播中的作用。高分辨率光学标测用于研究离体Langendorff灌注小鼠心脏的右心房和左心房附件的传导。研究了野生型（Cx40+/+）、杂合型（Cx40+/−）和敲除型（Cx40−/−）小鼠（包括成年和胚胎），以评估Cx40表达减少对不同起搏周期长度（100和60 ms）下窦房结功能和传导速度的影响。在成年和晚期胚胎Cx40+/+小鼠中，发现右心房和左心房附件之间的CV异质性。Cx40的部分（Cx40+/−）或完全（Cx40−/−）缺失与成年和胚胎小鼠的传导异质性丧失相关。此外，在交配后15.5天，发现Cx40−/−小鼠的窦房结冲动起始是异位的，而Cx40+/+小鼠显示出在界嵴附近发生的正常激活。我们的研究结果表明，Cx40起着至关重要的作用，在建立房间传导速度异质性的小鼠模型。此外，我们首次描述了正常窦房结冲动启动在性交后15.5天Cx40的发展要求。
Impulse propagation in cardiac tissue is a complex process in which intercellular coupling through gap junction channels is a critical component. Connexin40 (Cx40) is an abundant gap junction protein that is expressed in atrial myocytes. Alterations in the expression of Cx40 have been implicated in atrial arrhythmogenesis. The purpose of the current study was to assess the role of Cx40 in atrial impulse propagation. High-resolution optical mapping was used to study conduction in the right and left atrial appendages of isolated Langendorff-perfused murine hearts. Wild-type (Cx40+/+), heterozygous (Cx40+/−), and knockout (Cx40−/−) mice, both adult and embryonic, were studied to assess the effects of reduced Cx40 expression on sinus node function and conduction velocity at different pacing cycle lengths (100 and 60 ms). In both adult and late-stage embryonic Cx40+/+ mice, heterogeneity in CV was found between the right and left atrial appendages. Either partial (Cx40+/−) or complete (Cx40−/−) deletion of Cx40 was associated with the loss of conduction heterogeneity in both adult and embryonic mice. Additionally, sinus node impulse initiation was found to be ectopic in Cx40−/− mice at 15.5 days postcoitus, whereas Cx40+/+ mice showed normal activation occurring near the crista terminalis. Our findings suggest that Cx40 plays an essential role in establishing interatrial conduction velocity heterogeneity in the murine model. Additionally, we describe for the first time a developmental requirement for Cx40 in normal sinus node impulse initiation at 15.5 days postcoitus.