Contactin-2 expression in the cardiac Purkinje fiber network.
Contactin-2 expression in the cardiac Purkinje fiber network.
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DOI：
10.1161/circep.109.928820
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发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
Fishman GI
中科院分区：
文献类型：
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作者：
Pallante BA;Giovannone S;Fang-Yu L;Zhang J;Liu N;Kang G;Dun W;Boyden PA;Fishman GI
浦肯野细胞(Purkinje cell，PC)是心脏传导系统最末端的组成部分，其独特的电生理特性和浦肯野纤维网络的解剖复杂性可能是这些细胞在各种心律失常综合征的发生中发挥重要作用的原因。-对小鼠浦肯野纤维和工作的心室肌细胞进行差异转录图谱分析，以确定在PC中表达的新基因。浦肯野纤维中含量最高的转录本编码Contactin-2(Cntn2)，这是一种对神经元构型和离子通道聚集至关重要的细胞黏附分子。Cntn2在小鼠心室中的内源性表达仅限于心内膜下心肌细胞网络，在CCS-lacZ转基因小鼠中也表达β-半乳糖苷酶和连接蛋白40缝隙连接蛋白。Cntn2-LacZ敲门小鼠和Cntn2-EGFP BAC转基因报告小鼠都证实了Cntn2在浦肯野纤维网络中的表达，免疫组织化学染色也证实了单个犬浦肯野纤维的表达。Cntn2-EGFP+细胞的全细胞膜片钳记录和钙瞬变的测量表明，PC具有不同于心肌细胞的电生理特性，包括动作电位延长和频繁的后除极。Cntn2是专门化心脏传导系统的新标志物。Cntn2的内源性表达以及Cntn2依赖的转录报告提供了一个新的工具，通过它现在可以更容易地破译Purkinje细胞生物学和病理生理学。CCS中Contact蛋白家族成员的表达可能为浦肯野细胞内传导系统网络的图案化和离子通道的组织提供机制基础。
Purkinje cells (PCs) comprise the most distal component of the cardiac conduction system and their unique electrophysiological properties and the anatomic complexity of the Purkinje fiber network may account for the prominent role these cells play in the genesis of various arrhythmic syndromes. – Differential transcriptional profiling of murine Purkinje fibers and working ventricular myocytes was performed to identify novel genes expressed in PCs. The most highly enriched transcript in Purkinje fibers encoded Contactin-2 (Cntn2), a cell adhesion molecule critical for neuronal patterning and ion channel clustering. Endogenous expression of Cntn2 in the murine ventricle was restricted to a subendocardial network of myocytes that also express β-galactosidase in CCS-lacZ transgenic mice and the connexin40 gap junction protein. Both Cntn2-lacZ knockin mice and Cntn2-EGFP BAC transgenic reporter mice confirmed expression of Cntn2 in the Purkinje fiber network, as did immunohistochemical staining of single canine Purkinje fibers. Whole-cell patch-clamp recordings and measurements of Ca2+ transients in Cntn2-EGFP+ cells revealed electrophysiological properties indicative of PCs and distinctive from those of cardiac myocytes, including prolonged action potentials and frequent afterdepolarizations. Cntn2 is a novel marker of the specialized cardiac conduction system. Endogenous expression of Cntn2 as well as Cntn2-dependent transcriptional reporters provides a new tool through which Purkinje cell biology and pathophysiology can now more readily be deciphered. Expression of a contactin family member within the CCS may provide a mechanistic basis for patterning of the conduction system network and the organization of ion channels within Purkinje cells.