GAP JUNCTION PROTEIN PHENOTYPES OF THE HUMAN HEART AND CONDUCTION SYSTEM
GAP JUNCTION PROTEIN PHENOTYPES OF THE HUMAN HEART AND CONDUCTION SYSTEM
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DOI：
10.1111/j.1540-8167.1995.tb00357.x
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发表时间：
1995-10-01
影响因子：
2.7
通讯作者：
SAFFITZ, JE
中科院分区：
文献类型：
--
作者：
DAVIS, LM;RODEFELD, ME;SAFFITZ, JE
简介：间隙连接通道是心肌细胞间电流流动的细胞间阻力的主要决定因素。间隙连接的改变可能导致患者心律失常基质的发生。然而，哺乳动物心脏不同区域表达的间隙连接亚基蛋白（连接蛋白）的类型和数量存在显着的种间差异。为了阐明人类心脏传导特性的决定因素，我们对具有不同传导特性的特定人类心脏组织的连接蛋白表型进行了表征。方法和结果：使用单特异性抗体和窦房结和邻近心房、房室结和希氏束、束支以及左右心房的冰冻切片，通过免疫组织化学方法研究了 Cx37、Cx40、Cx43、Cx45 和 Cx46 的分布和相对丰度。心室壁。这些连接蛋白在人类心脏中的表达模式与之前的动物研究中的不同。窦房结间隙连接小而稀疏，含有 Cx45 和明显少量的 Cx40，但不含 Cx43。房室结间隙连接也很小，主要包含 Cx45 和 Cx40，但与窦房结不同，也表达 Cx43。心房间隙连接比节点连接大，并含有适量的 Cx40、Cx43 和 Cx45。束支的连接处尺寸最大，含有丰富的 Cx40、Cx43 和 Cx45。心室肌间隙连接主要含有Cx43和Cx45；在小到中型壁内冠状动脉的心内膜下肌细胞连接处和内皮细胞中仅检测到极少量的心室Cx40。偶尔在心房或心室肌细胞之间检测到最小的 Cx37 和 Cx46 免疫反应性。结论：在具有不同传导特性的人类心脏的特定区域中，各个连接蛋白的相对量以及间隙连接的数量和大小差异很大。这些差异可能在调节心脏传导速度方面发挥作用。在未来的心脏传导实验或建模研究中必须考虑人类心脏和实验动物心脏特定区域的连接蛋白表型的差异。
Introduction: Gap junction channels are major determinants of intercellular resistance to current flow between cardiac myocytes. Alterations in gap junctions may contribute to development of arrhythmia substrates in patients. However, there is significant interspecies variation in the types and amounts of gap junction subunit proteins (connexins) expressed in disparate regions of mammalian hearts. To elucidate determinants of conduction properties in the human heart, we characterized connexin phenotypes of specific human cardiac tissues with different conduction properties.Methods and Results: The distribution and relative abundance of Cx37, Cx40, Cx43, Cx45, and Cx46 were studied immunohistochemically using monospecific antibodies and frozen sections of the sinoatrial node and adjacent atria, the AV node and His bundle, the bundle branches, and the left and right ventricular walls. Patterns of expression of these connexins in the human heart differed from those in previous animal studies. Sinus node gap junctions were small and sparse and contained Cx45 and apparently smaller amounts of Cx40 but no Cx43. AV node gap junctions were also small and contained mainly Cx45 and Cx40 but, unlike the sinus node, also expressed Cx43. Atrial gap junctions were larger than nodal junctions and contained moderate amounts of Cx40, Cx43, and Cx45. Junctions in the bundle branches were the largest in size and contained abundant amounts of Cx40, Cx43, and Cx45. Gap junctions in ventricular myocardium contained mainly Cx43 and Cx45; only a very small amount of ventricular Cx40 was detected in subendocardial myocyte junctions and endothelial cells of small to medium sized intramural coronary arteries. Minimal Cx37 and Cx46 immunoreactivity was detected between occasional atrial or ventricular myocytes.Conclusions: The relative amounts of individual connexins and the number and size of gap junctions vary greatly in specific regions of the human heart with different conduction properties. These differences likely play a role in regulating cardiac conduction velocity. Differences in the connexin phenotypes of specific regions of the human heart and experimental animal hearts must be considered in future experimental or modeling studies of cardiac conduction.