Research on the development of biopacemaker by use of plnipotent P19CL6 cells.

近年来的分子生物学研究对心脏分化的转录因子和细胞生长因子进行了序列鉴定，并阐明了心肌细胞分化的机制。心肌细胞的分化是由细胞生长因子如BMP和ET-1诱导的，特定的转录因子（Csx/Nkx-2.5, GATA4, MEF2C）被激活。最后形成心肌细胞特异性蛋白（肌凝蛋白、肌动蛋白、离子通道）。然而，控制心脏离子通道表现的特定转录因子尚未阐明。此外，离子通道通过心肌兴奋-收缩耦合诱发动作电位的具体表现尚不清楚。另一方面，MAPK是通过MAPKKK和MAPKK的作用将细胞外信息传递给细胞信号的主要信号，与细胞分化和发育有关。我们分析了转录因子在多能性P19CL6细胞衍生的分化心肌细胞中传递的信号。P19CL6细胞在二甲亚砜（DMSO）作用下发育为心肌细胞并获得自动性。有丝分裂原活化蛋白激酶（MAPK）在心肌细胞分化和形态发生中起着重要作用。本研究回顾了影响P19CL6细胞起源-心肌细胞膜电流形成的细胞内信号，特别是离子通道的表现，通过MAPK。P19CL6细胞表达超极化激发内流（Ih）通道和两种Ca通道(I_<Ca。L >, I_ < Ca。T>)，显示出89 bpm的自动性。对于分化后的自动搏动和起搏器离子通道，p38-MAPK的抑制使细胞发育停止，未分化的P19CL6细胞未形成动作电位配置。此外，转录因子GATA4受到高度抑制。另一方面，经典的MAPK （ERK1/2,5）和JNK抑制下的肌细胞表现为83-108 bpm的自动，并观察到三种起搏器离子通道。因此，我们认为通过非经典MAPK或p38-MAPK传递的信号与P19CL6细胞分化阶段心脏起搏器离子通道的形成有关。这可能是一种潜在的生物起搏器理论，它可以控制靶肌细胞中的离子通道表达。因此，干预转录因子Csx/Nkx2.5成为鉴定离子通道表达和成熟机制的潜在靶点。少

Ttranscription factors on heart differentiation and cell growth factors are identified in sequence by recent molecular biology studies, and elucidating mechanism of cardiac muscle cell differentiation. Differentiation of a cardiac muscle cell is induced by cell growth factors such as BMP and ET-1, and specific transcription factors (Csx/Nkx-2.5, GATA4, MEF2C) are activated. Then cardiac muscle cell specific protein (myosin, actin, an ion channel) finally develops. However, a specific transcription factor that is to control manifestation of cardiac ion channels is not yet elucidated. In addition, the details of ion channel manifestation as a trigger for action potentials by means of myocardial excitation-contraction coupling are not clear. On the other hand, MAPK is a main signal conveying extracellular information to cellular signals via actions of MAPKKK and MAPKK, which are related to cell differentiation and development. We analyzed transcription factors to go through a signal in a … More cell concerned with current build-up in a differentiated cardiac muscle cell derived from pluripotent P19CL6 cells. P19CL6 cells developed into cardiac cells by dimethyl sulfoxide (DMSO) and acquires automaticity. It is known that mitogen-activated protein kinase (MAPK) plays an important role in cardiac muscle cell differentiation and morphogenesis. We reviewed a signal in the cell which affected the membrane current formation in a P19CL6 cell origin-cardiac muscle cell, ion channel manifestation, in particular, to go through MAPK by this study. A P19CL6 cell expresses hyperpolarization elicitation influx (Ih) channel and two kinds of Ca channels (I_<Ca. L>, I_<Ca. T>) after differentiated and shows automaticity of 89 bpm. As for the automatic beat and pacemaker ion channel after differentiation, cellular development was halted by inhibition of p38-MAPK, and action potential configuration was undeveloped from undifferentiated P19CL6 cells. Furthermore, transcription factor GATA4 was highly restrained. On the other hand, myocytes under infibition of classic MAPK (ERK1/2,5) and JNK showed automatic of 83-108 bpm, and three kinds of pacemaker ion channels were observed. Therefore, it is suggested that signals which go through nonclassical MAPK or p38-MAPK are was concerned with manifestation of developing pacemaker ion channels in differentiation stage to a cardiac muscle derived from P19CL6 cells. It may identify a potential theory of the bio-pacemaker which controls ion channel expression in targeted myocytes. Therefore, intervention of transcription factor Csx/Nkx2.5 becomes a potential target to identify the mechanism for ion channel expression and maturation. Less