Verheijck E E, Wessels A, van Ginneken A C, Bourier J, Markman M W, Vermeulen J L, de Bakker J M, Lamers W H, Opthof T, Bouman L N
Department of Physiology, Academic Medical Center, University of Amsterdam, The Netherlands.
Circulation. 1998 Apr 28;97(16):1623-31. doi: 10.1161/01.cir.97.16.1623.
In the sinoatrial node (SAN) the course of the action potential gradually changes from the primary pacemaker region toward the atrium. It is not known whether this gradient results from different intrinsic characteristics of the nodal cells, from an increasing electrotonic interaction with the atrium, or from both. Therefore we have characterized the immunohistochemical, morphological, and electrophysiological correlates of this functional gradient.
The distribution of rabbit nodal myocytes in the SAN has been studied by immunohistochemistry. After cell isolation, the electrophysiological characteristics of different nodal cell types were measured. (1) The staining pattern of a neurofilament protein coincides with the electrophysiologically mapped pacemaker region in the SAN. (2) Enzymatic digestion of the SAN reveals three morphologically different nodal cell types and one atrial type. Of each nodal cell type, neurofilament-positive as well as neurofilament-negative myocytes are found. Atrial cells are all neurofilament-negative. (3) In contrast to previous findings, we observed atrial cells in the very center of the SAN. The relative number of atrial cells gradually increases from the central pacemaker area toward the atrium. (4) Differences in electrophysiological characteristics between individual nodal cells are not associated with differences in cell type.
(1) The expression of neurofilaments can be used to delineate the nodal area in the intact SAN but is not sufficiently sensitive for characterizing all individual isolated nodal cells. (2) A fundamentally different organization of the SAN is presented: The gradual increase in density of atrial cells from the dominant area toward the crista terminalis in the SAN causes a gradual increase of atrial electrotonic influence that may be an important cause of the gradual transition of the nodal to the atrial type of action potential.
在窦房结(SAN)中,动作电位的过程从主要起搏区域向心房逐渐变化。目前尚不清楚这种梯度是由节点细胞不同的内在特性、与心房电紧张相互作用的增加,还是两者共同作用所致。因此,我们对这种功能梯度的免疫组织化学、形态学和电生理学相关性进行了表征。
通过免疫组织化学研究了兔窦房结中节点心肌细胞的分布。细胞分离后,测量了不同节点细胞类型的电生理特性。(1)神经丝蛋白的染色模式与窦房结中通过电生理学映射的起搏区域一致。(2)对窦房结进行酶消化后发现三种形态不同的节点细胞类型和一种心房细胞类型。每种节点细胞类型中,均发现了神经丝阳性和神经丝阴性的心肌细胞。心房细胞均为神经丝阴性。(3)与先前的研究结果相反,我们在窦房结的正中心观察到了心房细胞。从中央起搏区域到心房,心房细胞的相对数量逐渐增加。(4)单个节点细胞之间电生理特性的差异与细胞类型的差异无关。
(1)神经丝的表达可用于在完整的窦房结中勾勒节点区域,但对表征所有单个分离的节点细胞不够敏感。(2)提出了一种根本不同的窦房结组织结构:从窦房结的主要区域到终嵴,心房细胞密度逐渐增加,导致心房电紧张影响逐渐增加,这可能是节点动作电位逐渐转变为心房动作电位类型的重要原因。