2004 Fiscal Year Final Research Report Summary
Electrophysiological determination of P19CL6-derived cardiomyocytes and their modification by the transcription factor Csx/Nkx2-5
| Project/Area Number |
15590759
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Oita University (2004)
大分医科大学 (2003) |
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Principal Investigator |
ONO Katsushige Oita University, Faculty of Medicine, Professor, 医学部, 教授 (40253778)
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| Co-Investigator(Kenkyū-buntansha) |
LEE Tae-seong Oita University, Faculty of Medicine, Research Assistant, 医学部, 助手 (10336266)
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| Project Period (FY) |
2003 – 2004
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| Keywords | 分化心筋 / ion channel / 転写因子 / Csx / Nkx2.5 / GATA4 / MEF2C / 自動拍動 |
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| Research Abstract |
The homeobox-containing gene Csx/Nkx2-5 is one of cardiac-enriched transcription factors and it plays a critical role for early cardiogenesis. We investigated the effect of Csx/Nkx2-5 on the expression of cardiac ion channels with P19CL6-derived cardiomyocytes. P19CL6 cells and P19CL6 cells with Csx/Nkx2-5 overexpression(P19CL6-Csx cells) were efficiently differentiated into cardiomyocytes by a treatment with dimethyl sulfoxide. Action potentials and membrane currents were measured by whole cell patch clamp at distinct differentiation stage : the early stage(1-5 days after beating) and the late stage(10-15 days after beating). Spontaneous beating rate increased as differentiation advanced both in P19CL6 and P19CL6-Csx cell lines. Maximal diastolic potential of P19CL6-Csx cells was changed to more depolarized as differentiated. APD_<50> was shortened as differentiated in both cell lines. Cell size increased in P19CL6 cells. In P19CL6 cells, I_<to>,I_<Kr>,I_<Ks>,I_<K1>,I_<K,ACh>, where I_<K,ATP> were expressed from the early stage, and I_<to> was predominant in the all K^+ currents. By overexpression of Csx/Nkx2-5, developmental decrease of I_<to> was suppressed invariantly. Homeobox-containing gene Csx/Nkx2-5 modified the expression of cardiac ionic channels during differentiation period, dominantly in I_<to>.
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