In this study, an ion depleted zone created by an ion-selective membrane was used to impose a high and uniform constant extracellular potential over an entire ∼1000 cell rat cardiomyocyte (rCM) colony on-a-chip to trigger synchronized voltage-gated ion channel activities while preserving cell viability, thus extending single-cell voltage-clamp ion channel studies to an entire normalized colony. Image analysis indicated that rCM beating was strengthened and accelerated (by a factor of ∼2) within minutes of ion depletion and the duration of contraction and relaxation phases was significantly reduced. After the initial synchronization, the entire colony responds collectively to external potential changes such that beating over the entire colony can be activated or deactivated within 0.1 s. These newly observed collective dynamic responses, due to simultaneous ion channel activation/deactivation by a uniform constant-potential extracellular environment, suggest that perm-selective membrane modules on cell culture chips can facilitate studies of extracellular cardiac cell electrical communication and how ion-channel related pathologies affect cardiac cell synchronization. The future applications of this new technology can lead to better drug screening platforms for cardiotoxicity as well as platforms that can facilitate synchronized maturation of pluripotent stem cells into colonies with high electrical connectivity.

中文翻译：

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用片上离子消耗选择性渗透膜激活和同步心肌细胞集落的恒定电位环境

在这项研究中，由离子选择性膜产生的离子耗尽区用于在整个约 1000 细胞大鼠心肌细胞 (rCM) 片上集落施加高且均匀的恒定细胞外电位，以触发同步电压门控离子通道活动，同时保持细胞活力，从而将单细胞电压钳离子通道研究扩展到整个标准化集落。图像分析表明，在离子耗尽的几分钟内，rCM 跳动得到加强和加速（约 2 倍），并且收缩和松弛阶段的持续时间显着减少。初始同步后，整个菌落共同响应外部电位变化，从而可以在 0.1 秒内激活或停用整个菌落。这些新观察到的集体动态反应，由于均匀恒定电位的细胞外环境同时激活/失活离子通道，表明细胞培养芯片上的选择性渗透膜模块可以促进细胞外心肌细胞电通讯以及离子通道相关病理如何影响心肌细胞同步的研究。这项新技术的未来应用可以产生更好的心脏毒性药物筛选平台，以及可以促进多能干细胞同步成熟为具有高电连接性的集落的平台。表明细胞培养芯片上的选择性渗透膜模块可以促进细胞外心脏细胞电通讯以及离子通道相关病理如何影响心脏细胞同步的研究。这项新技术的未来应用可以产生更好的心脏毒性药物筛选平台，以及可以促进多能干细胞同步成熟为具有高电连接性的集落的平台。表明细胞培养芯片上的选择性渗透膜模块可以促进细胞外心脏细胞电通讯以及离子通道相关病理如何影响心脏细胞同步的研究。这项新技术的未来应用可以产生更好的心脏毒性药物筛选平台，以及可以促进多能干细胞同步成熟为具有高电连接性的集落的平台。