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小鼠心脏发育过程中心脏钠通道的组织分布和亚细胞定位

Tissue distribution and subcellular localization of the cardiac sodium channel during mouse heart development.

作者信息

Domínguez Jorge N, de la Rosa Angel, Navarro Francisco, Franco Diego, Aránega Amelia E

机构信息

Department of Experimental Biology, Faculty of Experimental Sciences, University of Jaén, Paraje de las Lagunillas, s/n, Jaén 23071, Spain.

出版信息

Cardiovasc Res. 2008 Apr 1;78(1):45-52. doi: 10.1093/cvr/cvm118. Epub 2008 Jan 4.

DOI:10.1093/cvr/cvm118
PMID:18178574
Abstract

AIMS

The aim of this study was to analyse the mRNA expression levels and protein distribution of the cardiac sodium channel Scn5a/Nav1.5 during mouse cardiogenesis.

METHODS AND RESULTS

Scn5a mRNA levels were determined by real-time RT-PCR using embryonic hearts ranging from E9.5 to E17.5 as well as postnatal and adult hearts. In addition, Scn5a protein (Nav1.5) distribution was analysed by immunohistochemistry and confocal microscopy. Scn5a mRNA levels displayed a peak at stage E11.5, decreased during the subsequent stages and then steadily increased from E17.5 onwards, and throughout the postnatal to the adult stages. Immunohistochemistry experiments revealed comparable distribution of Nav1.5 between the different cardiac chambers at early embryonic stages. During the foetal stages, Nav1.5 showed an enhanced expression in the trabeculated myocardium and in the bundle branches. At the subcellular level, Nav1.5 and Scn1b double-immunostaining analysis is consistent with the presence of both sodium channel subunits in the T-tubule system and the intercalated discs.

CONCLUSION

Our results demonstrate that the cardiac sodium channel, Nav1.5, shows a dynamic expression pattern during mouse heart development, indicating that it could play an important role in the acquisition of a mature pattern of conduction and contraction during cardiogenesis.

摘要

目的

本研究旨在分析心脏钠通道Scn5a/Nav1.5在小鼠心脏发生过程中的mRNA表达水平和蛋白质分布。

方法与结果

使用E9.5至E17.5的胚胎心脏以及出生后和成年心脏,通过实时逆转录聚合酶链反应(RT-PCR)测定Scn5a mRNA水平。此外,通过免疫组织化学和共聚焦显微镜分析Scn5a蛋白(Nav1.5)的分布。Scn5a mRNA水平在E11.5阶段出现峰值,在随后阶段下降,然后从E17.5开始稳步上升,并贯穿出生后至成年阶段。免疫组织化学实验显示,在胚胎早期不同心腔之间Nav1.5的分布具有可比性。在胎儿阶段,Nav1.5在小梁心肌和束支中表达增强。在亚细胞水平,Nav1.5和Scn1b双重免疫染色分析表明钠通道亚基在横管系统和闰盘中均有存在。

结论

我们的结果表明,心脏钠通道Nav1.5在小鼠心脏发育过程中呈现动态表达模式,表明它可能在心脏发生过程中成熟的传导和收缩模式的形成中发挥重要作用。

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