Morphological and functional heterogeniety of sinoatrial node pacemaker cells

尽管窦房结起搏细胞的电生理特性已经得到了很好的描述，但关于其不同的电特性的分子机制却知之甚少。本研究用免疫荧光技术研究了缝隙连接蛋白和K通道的表达和分布。1.缝隙连接蛋白在SA结节中的表达。结果表明：1)SA结节细胞不表达Cx43，但表达Cx45；3)有组织制备区，尤其是心内膜侧，细胞同时表达连接蛋白45和43。不同类型的连接蛋白在SA结点的表达以及少量小间隙连接的形成可能与SA结点细胞间耦合电导的降低有关。2.Kv1.5通道在SA结点的表达和定位。我们以前报道过4-AP对SA结点的电活动有显著影响。本研究对4-AP敏感的克隆性K通道之一Kv1.5通道在豚鼠SA结内及周围的分布进行了研究。Kv1.5在窦房结和心房肌均有丰富的表达，但两者的亚细胞分布不同。在心房肌，Kv1.5通道主要分布在与连接蛋白43紧密结合的盘间区，而在SA结节，Kv1.5通道更多地分布于细胞膜。Kv1.5通道在SA节点中的作用尚未完全确定，但它可能是4-AP对SA节点的显著影响的部分基础。

Although the electrophysiological properties of sinoatrial (SA) node pacemaker cells have been well characterized, only limited information is available about the molecular mechanisms underlying the distinct electrical properties. In the present study, the expression and distribution of gap junctional proteins and K+ channels have been studied by immunofluorescence techniques.1.Expression of connexins in the SA node.The rabbit SA node was stained with subtype-specific anti-connexin antibodies and was analyzed by confocal microscopy. The following results were obtained : 1)The SA node cells did not express connexin43 but did express connexin45.2)Connexin40 also appeared to be expressed by the SA node cells. 3)There were regions of tissue preparation, in particular, the endocardial side, in which the cells expressed both connexin45 and 43. The expression of different types of connexins in the SA node in addition to scarce formation of small gap junctions might be involved in the reduced intercellular coupling conductance between SA node cells.2.Expression and localization of the Kv1.5 channel in the SA node.We have previously reported that 4-AP has marked effects on the electrical activity of the SA node. In this study, the distribution of Kv1.5 channel, one of the 4-AP sensitive cloned K+ channels, has been studied in and around the guinea pig SA node. Kv1.5 was abundantly expressed in the SA node as well as the atrial muscle, although the subcellular distribution was different in the two tissues. In the atrial muscle, Kv1.5 channel was localized predominantly at the intercalated disk regions in close apposition with connexin43, whereas in the SA node Kv1.5 was more dispersed throughout the cell membrane. The role of the Kv1.5 channel in the SA node has not well established, but it may partly underlie the marked effects of 4-AP on the SA node.