Effects of diminished expression of connexin43 on gap junction number and size in ventricular myocardium

Effects of diminished expression of connexin43 on gap junction number and size in ventricular myocardium
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DOI:
10.1152/ajpheart.2000.278.5.h1662
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发表时间:
2000-05-01
影响因子:
4.8
通讯作者:
Yamada, KA
Yamada, KA
中科院分区:
医学2区
文献类型:
--
作者:
Saffitz, JE;Green, KG;Yamada, KA

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缝隙连接的数目和大小在心脏组织中差异很大,具有不同的传导推进力。关于细胞间连接的组织特异性模式是如何建立和调控的,我们知之甚少。为了阐明缝隙连接通道蛋白的表达与缝隙连接结构的关系,我们分析了Cx43+/-小鼠,这些小鼠主要的心室缝隙连接蛋白Cx43(Cx43)的表达存在遗传缺陷。定量共聚焦免疫荧光显微镜显示,Cx43+/-小鼠体内Cx43信号的减弱几乎完全是由于单个缝隙连接的数量减少(Cx43+/+和+/-脑室中分别为226+/-52和150+/-32个缝隙连接/视野;P<0.05)。两组单个缝隙连接的平均大小相同。免疫荧光结果经电子显微镜形态计量学证实。因此,当连接蛋白表达减弱时,心室肌细胞通过数量减少的大的、正常大小的缝隙连接而不是正常数量的较小的连接来相互连接。维持大间隙连接可能是一种支持安全的心室传导的适应性反应。
Gap junction number and size vary widely in cardiac tissues with disparate conduction propel-ties. Little is known about how tissue-specific patterns of intercellular junctions are established and regulated. To elucidate the relationship between gap junction channel protein expression and the structure of gap junctions, we analyzed Cx43 +/- mice, which have a genetic deficiency in expression of the major ventricular gap junction protein, connexin43 (Cx43). Quantitative confocal immunofluorescence microscopy revealed that diminished Cx43 signal in Cx43 +/- mice was due almost entirely to a reduction in the number of individual gap junctions (226 +/- 52 vs. 150 +/- 32 individual gap junctions/field in Cx43 +/+ and +/- ventricles, respectively; P < 0.05). The mean size of an individual gap junction was the same in both groups. Immunofluorescence results were confirmed with electron microscopic morphometry. Thus when connexin expression is diminished, ventricular myocytes become interconnected by a reduced number of large, normally sized gap junctions, rather than a normal number of smaller junctions. Maintenance of large gap junctions may be an adaptive response supporting safe ventricular conduction.