Analysis of the electrophysiological properties and arrhythmias in directly contacted skeletal and cardiac muscle cell sheets
Analysis of the electrophysiological properties and arrhythmias in directly contacted skeletal and cardiac muscle cell sheets
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DOI：
10.1016/j.cardiores.2005.03.014
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发表时间：
2005-08-15
影响因子：
10.8
通讯作者：
Ogawa, S
中科院分区：
文献类型：
--
作者：
Itabashi, Y;Miyoshi, S;Ogawa, S
目的：自体骨骼肌细胞移植到活体心脏有时会导致严重的心律失常。本研究的目的是利用最新发展的细胞片工程技术，研究心肌细胞(CM)与心肌细胞(SM)直接接触的电生理学，探讨其导致心律失常的机制。方法：制备原代培养的新生大鼠心肌细胞(SM)和心肌细胞(CM)，并用温度响应型培养皿制备细胞片。用常规微电极记录动作电位。分别用Fluo-3和di-4-ANEPPS记录细胞内钙离子浓度和动作电位的光学标测图像。采用视频运动检测系统检测心律失常。结果：SM肌管偶有显示自律性。肌片没有显示同步收缩，而是成组的肌管独立收缩。通过人工起搏诱导的SM的动作电位不会扩展到整个电极片，而是限制在电极周围的一个有限的小区域内，并且在CM和SM片之间产生电连接或传播动作电位是不可行的。部分肌管呈现自律性收缩的SM膜可引起共培养CM膜的纤颤样收缩，这种心律失常可被牵张激活的通道阻滞剂GsMTx-4特异性阻断。结论：SM膜不能与周围CM膜同步收缩或产生功能性合胞，可能是由于SM自发收缩所致的牵张引起的心律失常。(C)2005年欧洲心脏病学会。爱思唯尔出版，版权所有。
Objective: Autologous skeletal muscle cell (SM) transplantation into the in vivo heart sometimes induces serious arrhythmias. The purpose of this study was to investigate the electrophysiology of cardiomyocyte (CM) and SM in direct contact and to study the mechanism underlying the cause of arrhythmia using the recently developed cell sheet engineering technique.Methods: Primary cultured rat neonatal SM and CM were prepared, and cell sheets were fabricated using temperature-responsive culture dishes. The action potential was recorded by a conventional microelectrode. Intracellular calcium concentration and optical mapping image of the action potential were recorded using Fluo-3 and di-4-ANEPPS, respectively. A video motion-detecting system was used for the detection of arrhythmias.Results: SM myotubes occasionally displayed automaticity. SM sheets did not display synchronized contraction, but instead groups of myotubes contracted independently. The action potential of SM, induced by artificial pacing, did not expand to the entire sheet but was limited within a restricted, small area around the electrode, and it was unfeasible to generate an electrical connection or propagate an action potential between CM and SM sheets. SM sheets, in which some of the myotubes displayed automaticity, caused fibrillation-like contraction in the co-cultured CM sheets, and this arrhythmia was specifically blocked by the stretch-activated channel blocker GsMTx-4.Conclusions: These findings show that SM sheets do not contract synchronously or generate functional syncytia with the surrounding CM sheets and that stretch-induced arrhythmias due to spontaneous contraction of SM may occur in the CM sheet. (C) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.