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The sophisticated architecture of the rat atrioventricular node

Yoo, Shin (2005) The sophisticated architecture of the rat atrioventricular node. PhD thesis, University of Leeds.

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Abstract

In the mammalian heart, the action potential spontaneously generated in the sinoatrial (SA) node propagates through the atria to reach the atrioventricular (AV) node. As the only conduction pathway between the atria and ventricles, the AV node functions to delay and regulate action potential conduction between the atria and ventricles. Since Tawara described the anatomical and morphological characteristics of the AV node in 1906, it has been difficult to correlate electrophysiological recordings with distinct cell types and the three dimensional structure of the AV node due to the exceptional functional and architectural complexity of this region. The cardiac voltage-gated Na+ channel isoform (Na1.5) is known to play a major role in the generation and conduction of the action potential in the heart. Recently, various mutations of Na, 1.5 responsible for AV conduction block and Na,, 1.5+/- mice with impaired AV conduction have been reported. Various neuronal Na' channel isoforms have also been shown to be expressed in the heart (mouse ventricular myocytes and rat and mouse SA node) and to be functionally important. The distribution of neuronal Na channel isoforms in the AV node is unknown. The aim of this study was to investigate the distribution of cardiac and neuronal Na'channel isoforms in and around the AV node. The nodal cell region was identified by Masson's trichrome staining and confocal microscopy with immunohistochemical markers, such as connexin43 (Cx43), desmoplakin(DP), atrial natriuretic peptide (ANP) and the type 4 hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel. The unique pattern of expression in the nodal cell region (DP-positive/Cx43-negative/ANP-negative/HCN4-positive) allowed it to be distinguished from the surrounding working myocardium (DP-positive/Cx43-positive/HCN4-negative). I have investigated the expression of Na,1.5 and other Na+ channel isoforms in rat AV node. Na1.1 was distributed in a similar manner to Na1.5, Na1.2 was not detected. Na1.3 labelling was restricted to nerve fibres and nerve cell bodies and was not detected in myocytes.Na1.3 labelling was abundant in the enclosed node and the common bundle, but much less abundant in other regions. Na1.4, the skeletal isoform, was not studied. Na1.5 labelling was present in atrial and ventricular myocardium and the left bundle branch (right not studied). However, Na1.5 labelling was absent in the open node, the enclosed node and the common bundle, but present at a reduced level in the posterior nodal extension, transitional cells and AV ring bundle. Na 1.6 was not detected. The study has revealed a complex organisation of three different myocyte types at the AV junction (including the tricuspid annulus). Impaired AV conduction as a result of mutations in or loss of Na1.5 must be the result of impaired conduction in the AV node inputs (posterior nodal extension and transitional cells) or output (bundle branch) rather than the AV node itself (open and enclosed nodes).

Item Type: Thesis (PhD)
Academic Units: The University of Leeds > Faculty of Biological Sciences (Leeds)
Depositing User: Ethos Import
Date Deposited: 19 Feb 2010 11:06
Last Modified: 19 Sep 2013 15:02
URI: http://etheses.whiterose.ac.uk/id/eprint/452

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