Dissociated spatial patterning of gap junctions and cell adhesion junctions during postnatal differentiation of ventricular myocardium
Dissociated spatial patterning of gap junctions and cell adhesion junctions during postnatal differentiation of ventricular myocardium
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DOI：
10.1161/01.res.80.1.88
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发表时间：
1997-01-01
影响因子：
20.1
通讯作者：
Gourdie, RG
中科院分区：
文献类型：
--
作者：
Angst, BD;Khan, LUR;Gourdie, RG
心肌细胞间缝隙连接的空间分布不均匀性是影响工作心肌电机械功能的重要因素。病变心肌细胞间电连接的正常几何结构的破坏与折返、心律失常和传导障碍相关。目前，决定正常心肌间隙连接组织中这种精确空间顺序的发育机制尚不清楚。为了研究这个问题，我们使用免疫电子和免疫共聚焦显微镜分析啮齿动物和犬左心室心肌成熟过程中间隙连接（连接蛋白43），桥粒（桥粒斑蛋白）和粘附连接（N-钙粘蛋白）成分的空间分布。在大鼠中，在出生后的前20天内，缝隙连接和细胞粘附连接的分布出现了显着的分歧。结果发现，尽管间隙连接最初表现出分散分布在肌细胞膜上，但桥粒和粘附连接在出生后表现出更快的向细胞末端（新生闰盘）极化。在随后的出生后发育（出生后20至90天），缝隙连接逐渐集中在这些细胞粘附连接丰富的膜区。对15胎龄和出生后1、5、10、20、40、70和90天的一系列大鼠的这一过程的定量分析表明，
Nonuniformity in the spatial patterning of gap junctions between heart muscle cells is now recognized as an important determinant of electromechanical function in working myocardium. Breakdown of the normal geometry of electrical intercellular connectivity in diseased myocardium correlates with reentry, arrhythmia, and conduction disturbance. The developmental mechanism(s) that determines this precise spatial order in gap junction organization in normal myocardium is at present unknown. To examine this question, we have used immunoelectron and immunoconfocal microscopy to analyze the spatial distributions of gap junctional (connexin43), desmosomal (desmoplakin), and adherens junctional (N-cadherin) components during maturation of rodent and canine left ventricular myocardium. In rats, a striking divergence in the distribution of gap junctions and cell adhesion junctions emerged within the first 20 days of postnatal life. It was found that although gap junctions initially demonstrated dispersed distributions across myocyte cell membranes, desmosomes and adherens junctions showed more rapid polarization toward cell termini tie, nascent intercalated disks) after birth. Over subsequent postnatal development (20 to 90 postnatal days), gap junctions became progressively concentrated in these cell adhesion junction-rich zones of membrane. Quantitative analyses of this process in a series of rats aged 15 embryonic and 1, 5, 10, 20, 40, 70, and 90 postnatal days indicated that significantly higher levels (P