Verheijck E E, van Kempen M J, Veereschild M, Lurvink J, Jongsma H J, Bouman L N
Academic Medical Center, University of Amsterdam, Task Force Heart Failure and Aging, Department of Physiology, P.O. Box 22700, 1100 DE, Amsterdam, The Netherlands.
Cardiovasc Res. 2001 Oct;52(1):40-50. doi: 10.1016/s0008-6363(01)00364-9.
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.
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 ( approximately 100 microm). 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.
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.
窦房（SA）结由相对少量耦合不佳的细胞组成。目前尚不清楚这些起搏细胞如何驱动周围心房，同时又免受其超极化影响。为了在小组织尺度上探讨这个问题，我们研究了小鼠SA结区域的激活模式，并将该模式与不同缝隙连接蛋白，即连接蛋白（Cx）37、Cx40、Cx43和Cx45的分布相关联。
使用传统微电极技术对小鼠SA结进行电生理标测。主要起搏区域位于终嵴外侧和内侧肢之间的角部。单灶起搏发生在由450个细胞组成的一组起搏纤维中。在结区，在小距离（约100微米）内观察到结性和心房波形的转变。激活模式与连接蛋白分布之间的相关性显示，在主要和次要起搏区域，抗Cx45有广泛标记。在这些结区内未发现Cx45标记的梯度。在终嵴表达Cx40和Cx43的心肌细胞与结区表达Cx45的心肌细胞之间发现了明显的转变。此外，标记有Cx43和Cx40的心肌细胞束突入结区。Cx37标记仅存在于内皮细胞之间。此外，一条结缔组织带在很大程度上分隔了结组织和心房组织。
我们的结果表明，Cx43和Cx40阳性的心房细胞束突入Cx45阳性的结区，并且一条结缔组织带在很大程度上分隔了结组织和心房组织。小鼠SA结的这种组织结构提供了一种结构基础，既能保护结区免受心房超极化影响，又能使动作电位从结区快速传导至周围心房。
