Electrophysiological features of the mouse sinoatrial node in relation to connexin distribution

Objective: The sinoatrial (SA) node consists of a relatively small number o f 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 h yperpolarizing influence. To explore this issue on a small tissue scale we studied the activation pattern of the mouse SA node region and correlated t his pattern with the distribution of different gap junction proteins, conne xin (Cx)37, Cx40, Cx43 and Cx45. Methods and Results: The mouse SA node was electrophysiologically mapped using a conventional microelectrode techniqu e. 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 tra nsitions of nodal and atrial waveform were observed over small distances (s imilar to 100 mum). Correlation between the activation pattern and connexin distribution revealed extensive labeling by anti-Cx45 in the primary and s econdary pacemaker area. Within these nodal areas no gradient in Cx45 label ing was found. A sharp transition was found between Cx40- and Cx43-expressi ng myocytes of the crista terminalis and the Cx45-expressing myocytes of th e node. In addition, strands of myocytes labeled for Cx43 and Cx40 protrude into the nodal area. Cx37 labeling was only present between endothelial ce lls. Furthermore, a band of connective tissue largely separates the nodal f rom the atrial tissue. Conclusions: Our results demonstrate strands of Cx43 and Cx40 positive atrial cells protruding into the Cx45 positive nodal are a and a band of connective tissue largely separating the nodal and atrial t issue. This organization of the mouse SA node provides a structural substra te that both shields the nodal area from the hyperpolarizing influence of t he atrium and allows fast action potential conduction from the nodal area i nto the surrounding atrium. (C) 2001 Elsevier Science B.V. All rights reser ved.