Published online before print April 2, 2009, doi: 10.1161/CIRCEP.108.803569
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Original Articles |
Ion Channel Transcript Expression at the Rabbit Atrioventricular Conduction Axis
From the Cardiovascular Research Group (I.D.G., J.O.T., H.D., M.R.B.), Faculty of Medical and Human Sciences, University of Manchester, Core Technology Facility, Manchester, United Kingdom; the Department of Circulation (M.Y.), Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan; Institute of Membrane and Systems Biology (G.M.G.), University of Leeds, Leeds, United Kingdom; and Centre for Integrated Systems Biology (R.B.), University of Nottingham, Nottingham, United Kingdom.
Correspondence to M.R. Boyett, PhD, University of Manchester, Core Technology Facility, 46 Grafton St, Manchester M13 9NT, UK. E-mail mark.boyett{at}manchester.ac.uk
Received January 28, 2008; accepted February 4, 2009.
Background— Little is known about the distribution of gap junctions and ion channels in the atrioventricular node, even though the physiology and pathology of the atrioventricular node is ultimately dependent on them.
Methods and Results— The abundance of 30 transcripts for markers, gap junctions, ion channels, and Ca2+-handling proteins in different regions of the rabbit atrioventricular node (nodal extension and proximal and distal penetrating bundle of His as well as atrial and ventricular muscle) was measured using a novel quantitative polymerase chain reaction technique and in situ hybridization. The expression profile of the nodal extension (slow pathway into penetrating bundle) was similar to that of the sinoatrial node. For example, in the nodal extension, in contrast to the atrial muscle and as expected for a slowly conducting tissue with pacemaker activity, there was no or reduced expression of Cx43, Nav1.5, Cav1.2, Kv1.4, KChIP2, and RYR3 and high expression of Cav1.3 and HCN4. The expression profile of the penetrating bundle was less specialized. In situ hybridization revealed a transitional zone with reduced expression of Cx43, Nav1.5, and KChIP2 that may form the fast pathway into the penetrating bundle.
Conclusions— At the atrioventricular node, the expression of gap junctions and ion channels in the nodal extension (slow pathway) and a transitional zone (putative fast pathway) as well as the penetrating bundle (output pathway) is specialized and heterogeneous and roughly matches the electrophysiology of the different regions.
Key Words: atrioventricular node • conduction system • ion channels • connexins • qPCR • in situ hybridization
CLINICAL PERSPECTIVE
Drs Billeter and Boyett are joint senior authors.The online-only Data Supplement is available at http://circep.ahajournals.org/cgi/content/full/CIRCEP.108.803569/DC1.