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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Gene Expression Regulation, Developmental*
  • Heart / embryology*
  • Heart / growth & development*
  • Immunohistochemistry
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Confocal
  • Myocardium / cytology
  • Myocardium / metabolism*
  • NAV1.5 Voltage-Gated Sodium Channel
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*
  • Tissue Distribution
  • Voltage-Gated Sodium Channel beta-1 Subunit

Substances

  • NAV1.5 Voltage-Gated Sodium Channel
  • RNA, Messenger
  • Scn1b protein, mouse
  • Scn5a protein, mouse
  • Sodium Channels
  • Voltage-Gated Sodium Channel beta-1 Subunit