Electromechanical coupling between skeletal and cardiac muscle. Implications for infarct repair.
Electromechanical coupling between skeletal and cardiac muscle. Implications for infarct repair.
复制标题
骨骼肌和心肌之间的机电耦合。对梗塞修复的影响。
DOI：
10.1083/jcb.149.3.731
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发表时间：
2000-05-01
影响因子：
7.8
通讯作者：
Murry, C E
中科院分区：
文献类型：
--
作者：
Reinecke, H;MacDonald, G H;Hauschka, S D;Murry, C E
骨骼肌母细胞在受伤的心脏中形成成熟肌肉的移植物，这些移植物在外源性刺激下收缩。然而，目前尚不清楚心肌能否与骨骼肌形成机电连接并诱导其同步收缩。在这里，我们报道了未分化的大鼠骨骼肌母细胞表达N-钙粘蛋白和连接蛋白43，这两种蛋白是间盘的主要黏附和缝隙连接蛋白，但在分化为肌管后这两种蛋白的表达明显下调。同样，受损心脏中分化的骨骼肌移植物没有检测到N-钙粘附素或连接蛋白43；因此，体内移植后不会发生机电耦合。相反，当新生或成年心肌细胞与骨骼肌共培养时，∼10%的骨骼肌管与相邻的心肌细胞同步收缩。异丙肾上腺素使共培养的肌管收缩速度增加25%，而不影响单一培养的肌管，表明心肌细胞是起搏器。缝隙连接抑制剂庚醇终止了肌管的收缩，但使单个心肌细胞的自发收缩保持不变，表明肌管是通过缝隙连接激活的。共聚焦显微镜显示，在体外培养的新生或成年心肌细胞与肌管连接处有钙粘蛋白和连接蛋白43的表达。微量注射后，肌管通过缝隙连接将染料转移到新生心肌细胞。钙成像显示心肌细胞和肌管内同步的钙瞬变。因此，心肌细胞可以与一些骨骼肌管在共培养中形成机电连接，并通过缝隙连接诱导它们的同步收缩。虽然机制尚不清楚，但如果在体内可以诱导出类似的连接，它们可能足以使骨骼肌移植物与宿主心肌同步跳动。
Skeletal myoblasts form grafts of mature muscle in injured hearts, and these grafts contract when exogenously stimulated. It is not known, however, whether cardiac muscle can form electromechanical junctions with skeletal muscle and induce its synchronous contraction. Here, we report that undifferentiated rat skeletal myoblasts expressed N-cadherin and connexin43, major adhesion and gap junction proteins of the intercalated disk, yet both proteins were markedly downregulated after differentiation into myo-tubes. Similarly, differentiated skeletal muscle grafts in injured hearts had no detectable N-cadherin or connexin43; hence, electromechanical coupling did not occur after in vivo grafting. In contrast, when neonatal or adult cardiomyocytes were cocultured with skeletal muscle, ∼10% of the skeletal myotubes contracted in synchrony with adjacent cardiomyocytes. Isoproterenol increased myotube contraction rates by 25% in coculture without affecting myotubes in monoculture, indicating the cardiomyocytes were the pacemakers. The gap junction inhibitor heptanol aborted myotube contractions but left spontaneous contractions of individual cardiomyocytes intact, suggesting myotubes were activated via gap junctions. Confocal microscopy revealed the expression of cadherin and connexin43 at junctions between myotubes and neonatal or adult cardiomyocytes in vitro. After microinjection, myotubes transferred dye to neonatal cardiomyocytes via gap junctions. Calcium imaging revealed synchronous calcium transients in cardiomyocytes and myotubes. Thus, cardiomyocytes can form electromechanical junctions with some skeletal myotubes in coculture and induce their synchronous contraction via gap junctions. Although the mechanism remains to be determined, if similar junctions could be induced in vivo, they might be sufficient to make skeletal muscle grafts beat synchronously with host myocardium.