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Molecular mapping of the rabbit atrioventricular node

Greener, Ian David (2006) Molecular mapping of the rabbit atrioventricular node. PhD thesis, University of Leeds.

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Abstract

The atrioventricular node (AVN) of the heart is responsible for the important conduction delay between atrial systole and ventricular systole. The anatomical architecture and functional properties of the AVN are complex. Ionic currents have been characterised in the AVN at both the whole tissue level and single cell level. However, little is known about the molecular basis of these ionic currents. There were two aims of this research: 1) to generate an accurate three-dimensional reconstruction of the rabbit AVN conduction axis and 2) to use real time PCR and in situ hybridisation to measure levels of mRNA for specific ion channels and membrane proteins in the rabbit AVN and surrounding atrial and ventricular tissue. Neurofilament-M (NF-M) immunolabelling revealed a tract of cells extending from the posterior nodal extension through the compact node to the common bundle. The PNE appeared to correspond to the slow pathway. Loosely packed atrial muscle comprised the anterior region of the AVN conduction axis closest to the enclosed part of the AVN and most likely represents the fast pathway. Lower nodal cells extended from the common bundle to the lower extremities of the compact node and PNE. Significant differences in the mRNA levels between the PNE and atrial muscle for the pacemaker channel HCN4, INa channels Navl. 1 and Na, 1.5, the Ica,L channel Cav 1.3, the I to channel ß-subunit KChIP2 and Cx43 were found HCNI, Nav 1.1, Cav 1.3 and NF-M mRNA were significantly higher in the PNE, compact node and common bundle compared to the atrium and ventricle. Kir 2.1 mRNA was significantly higher in the ventricular muscle compared to the PNE and atrial muscle. Atrial natriuretic peptide (ANP) mRNA, was significantly higher in the atrial muscle compared to other tissues. For mRNAs for the Ito channels, Kv 4.2 and Kv 4.3, the delayed rectifier K+ channels, Kv 1.5, ERG, K, LQTI and minK, the inward rectifier K+ channels, Kir 2.2, Kir6.2 and ß-subunit SUR2A, and the Ca2+ handling proteins, RYR2, RYR3, NCXI and SERCA2a, there were no significant differences between tissues. In situ hybridisation staining revealed further complexity of the AVN conduction axis tissue. A region of loosely packed atrial tissue immediately adjacent to the nodal tissue was KChIP2 negative and Nav1.5 negative, and the lower nodal cells were both Cav 1.2 and Cav 1.3 positive. This study has described a complex architecture of the AVN and added further complexity by providing a detailed account of ion channel expression throughout this tissue.

Item Type: Thesis (PhD)
Academic Units: The University of Leeds > Faculty of Biological Sciences (Leeds)
Depositing User: Ethos Import
Date Deposited: 19 Feb 2010 14:29
Last Modified: 04 Sep 2013 09:42
URI: http://etheses.whiterose.ac.uk/id/eprint/220

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