| Co-Investigator(Kenkyū-buntansha) |
LEE Tae-seong Oita University, Faculty of Medicine, Research Assistant, 医学部, 助手 (10336266)
KAKU Toshihiko Oita University, Faculty of Medicine, Research Assistant, 医学部, 助手 (40372792)
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| Research Abstract |
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
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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
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