Conversion of Ca2+ oscillation into propagative electrical signals by Ca2+-activated ion channels and connexin as a reconstituted Ca2+ clock model for the pacemaker activity
Conversion of Ca2+ oscillation into propagative electrical signals by Ca2+-activated ion channels and connexin as a reconstituted Ca2+ clock model for the pacemaker activity
复制标题
通过 Ca2 激活的离子通道和连接蛋白将 Ca2 振荡转换为传播电信号，作为起搏器活动的重建 Ca2 时钟模型
DOI：
10.1016/j.bbrc.2019.01.080
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发表时间：
2019
影响因子：
3.1
通讯作者：
Imaizumi Yuji
中科院分区：
文献类型：
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作者：
Saeki Takanori;Kimura Taisuke;Hashidume Keigo;Murayama Takashi;Yamamura Hisao;Ohya Susumu;Suzuki Yoshiaki;Nakayama Shinsuke;Imaizumi Yuji
细胞内Ca 2+信号转化为电活性导致多种不同的生理影响，这取决于细胞类型。在某些器官如胃肠和泌尿系统中，起搏细胞中的自发性Ca 2+振荡本质上可以作为Ca 2+钟机制发挥作用，这最初是在心脏窦房结细胞的起搏中发现的。离散的Ca 2+时钟事件到自发电活动的转换是通过多细胞器官启动和传播起搏器活动的重要步骤，从而导致同步的生理功能。在此，在HEK 293细胞中重建了从Ca 2+振荡到电慢波启动及其传播的细胞内信号转导模型。这是基于兰尼碱受体（RyR）3型、Ca 2+激活的离子通道（即小电导Ca 2+激活的K+通道（SK 2）或Ca 2+激活的Cl−通道（TMEM 16 A））和连接蛋白43异源共表达来实现的。分别用表达通道的选择性阻断剂和间隙连接抑制剂18β-大黄酸处理，电波的传播被消除或显著减少。因此，我们证明，钙离子振荡的电信号与细胞到细胞的传播的转换可以重建作为一个模型的钙离子时钟起搏器活性的关键元件在异源表达系统中的组合表达。
Conversion of intracellular Ca2+signals to electrical activity results in multiple and differing physiological impacts depending on cell types. In some organs such as gastrointestinal and urinary systems, spontaneous Ca2+oscillation in pacermaker cells can function essentially as a Ca2+clock mechanism, which has been originally found in pacemaking in sinoatrial node cell of the heart. The conversion of discrete Ca2+clock events to spontaneous electrical activity is an essential step for the initiation and propagation of pacemaker activity through the multicellular organs resulting in synchronized physiological functions. Here, a model of intracellular signal transduction from a Ca2+oscillation to initiation of electrical slow waves and their propagation were reconstituted in HEK293 cells. This was accomplished based on ryanodine receptor (RyR) type 3, Ca2+-activated ion channels, i.e. small conductance Ca2+-activated K+channel (SK2) or Ca2+-activated Cl−channel (TMEM16A), and connexin43 being heterologously co-expressed. The propagation of electrical waves was abolished or substantially reduced by treatment with selective blockers of the expressed channels and 18β-glycyrrhetinic acid, a gap junction inhibitor, respectively. Thus, we demonstrated that the conversion of Ca2+oscillation to electrical signals with cell to cell propagation can be reconstituted as a model of Ca2+clock pacemaker activity by combinational expression of critical elements in heterologous expression system.