Molecular architecture of the human specialised atrioventricular conduction axis

I. D. Greener, O. Monfredi, S. Inada, N. J. Chandler, J. O. Tellez, A. Atkinson, M. A. Taube, R. Billeter, R. H. Anderson, I. R. Efimov, P. Molenaar, D. C. Sigg, V. Sharma, M. R. Boyett, H. Dobrzynski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

The atrioventricular conduction axis, located in the septal component of the atrioventricular junctions, is arguably the most complex structure in the heart. It fulfils a multitude of functions, including the introduction of a delay between atrial and ventricular systole and backup pacemaking. Like any other multifunctional tissue, complexity is a key feature of this specialised tissue in the heart, and this complexity is both anatomical and electrophysiological, with the two being inextricably linked. We used quantitative PCR, histology and immunohistochemistry to analyse the axis from six human subjects. mRNAs for ~50 ion and gap junction channels, Ca2+-handling proteins and markers were measured in the atrial muscle (AM), a transitional area (TA), inferior nodal extension (INE), compact node (CN), penetrating bundle (PB) and ventricular muscle (VM). When compared to the AM, we found a lower expression of Nav1.5, Kir2.1, Cx43 and ANP mRNAs in the CN for example, but a higher expression of HCN1, HCN4, Cav1.3, Cav3.1, Kir3.4, Cx40 and Tbx3 mRNAs. Expression of some related proteins was in agreement with the expression of the corresponding mRNAs. There is a complex and heterogeneous pattern of expression of ion and gap junction channels and Ca2+-handling proteins in the human atrioventricular conduction axis that explains the function of this crucial pathway.

Original languageEnglish (US)
Pages (from-to)642-651
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume50
Issue number4
DOIs
StatePublished - Apr 2011
Externally publishedYes

Keywords

  • Arrhythmias
  • Atrioventricular node
  • Gap junctions
  • Ion channels

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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