© 2001 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Electrophysiological features of the mouse sinoatrial node in relation to connexin distribution
aAcademic Medical Center, University of Amsterdam, Task Force Heart Failure and Aging, Department of Physiology, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands
bUniversity Medical Center Utrecht, Department of Medical Physiology, 3584 CG Utrecht, The Netherlands
* Corresponding author. Tel.: +31-20-566-4670; fax: +31-20-691-9319 e.verheijck{at}amc.uva.nl
Objective: The sinoatrial (SA) node consists of a relatively small number of poorly coupled cells. It is not well understood how these pacemaker cells drive the surrounding atrium and at the same time are protected from its hyperpolarizing influence. To explore this issue on a small tissue scale we studied the activation pattern of the mouse SA node region and correlated this pattern with the distribution of different gap junction proteins, connexin (Cx)37, Cx40, Cx43 and Cx45. Methods and Results: The mouse SA node was electrophysiologically mapped using a conventional microelectrode technique. The primary pacemaker area was located in the corner between the lateral and medial limb of the crista terminalis. Unifocal pacemaking occurred in a group of pacemaking fibers consisting of 450 cells. In the nodal area transitions of nodal and atrial waveform were observed over small distances (
100 µm). Correlation between the activation pattern and connexin distribution revealed extensive labeling by anti-Cx45 in the primary and secondary pacemaker area. Within these nodal areas no gradient in Cx45 labeling was found. A sharp transition was found between Cx40- and Cx43-expressing myocytes of the crista terminalis and the Cx45-expressing myocytes of the node. In addition, strands of myocytes labeled for Cx43 and Cx40 protrude into the nodal area. Cx37 labeling was only present between endothelial cells. Furthermore, a band of connective tissue largely separates the nodal from the atrial tissue. Conclusions: Our results demonstrate strands of Cx43 and Cx40 positive atrial cells protruding into the Cx45 positive nodal area and a band of connective tissue largely separating the nodal and atrial tissue. This organization of the mouse SA node provides a structural substrate that both shields the nodal area from the hyperpolarizing influence of the atrium and allows fast action potential conduction from the nodal area into the surrounding atrium.
KEYWORDS Cell communication; Conduction system; Gap junctions; Sinus node
1 E. Etienne Verheijck and Marjan J.A. van Kempen contributed equally to this study.
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