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Electrophysiological determination of P19CL6-derived cardiomyocytes and their modification by the transcription factor Csx/Nkx2-5

Electrophysiological determination of P19CL6-derived cardiomyocytes and their modification by the transcription factor Csx/Nkx2-5
P19CL6 来源的心肌细胞的电生理测定及其转录因子 Csx/Nkx2-5 的修饰
批准号:
15590759
负责人:
ONO Katsushige
金额:
$1.92万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
2003
资助国家:
日本
项目状态:
已结题
起止时间:
2003 至 2004

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中文摘要
翻译
同源异型盒基因CSX/Nkx2-5是一种心脏富集型转录因子,在早期心脏发生中起着关键作用。我们研究了CSX/Nkx2-5对P19CL6来源的心肌细胞心肌离子通道表达的影响。二甲基亚砜可使P19CL6细胞和CSX/Nkx2-5高表达的P19CL6细胞(P19CL6-CSX细胞)有效地分化为心肌细胞。在不同分化阶段:早期(搏动后1~5d)和晚期(搏动后10~15d),用全细胞膜片钳技术测定动作电位和膜电流。在P19CL6和P19CL6-CSX细胞系中,自发搏动频率随着分化的推进而增加。随着细胞分化,P19CL6-CSX细胞的最大舒张期电位改变为去极化。在分化过程中,两种细胞系的APD50均缩短。P19CL6细胞体积增大。在P19CL6细胞中,I_<to>,I_<Kr>,I_<Ks>,I_<K1>,I_<K,ACh>,其中I_<K,ATP>;通过CSX/Nkx2-5的过度表达,Itt;to Gt;的发育性降低一直受到抑制。同源异型盒基因CSX/Nkx2-5在分化期改变心脏离子通道的表达,主要发生在It1~Gt;。
英文摘要
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>.
期刊论文(16)
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会议论文
小野克重: "もの知り図鑑 顕微鏡で探る不思議な世界 第5巻"健学社. 150 (2004)
小野胜成:“知识图解指南:用显微镜探索神秘世界第 5 卷”Kengakusha(2004 年)。
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Na^+チャネルの病態生理学 -分子構造に依存する開閉機構と遺伝性疾患との関わり-
Na^+通道的病理生理学 - 取决于分子结构的打开/关闭机制及其与遗传疾病的关系 -
DOI: --
发表时间: 2003
期刊: 心臓 35(6)
影响因子: --
作者: [Kaku T, Lee TA, Arita M, Hadama T, Ono K, 小野克重]
通讯作者: 小野克重
Kaku T: "The gating and conductance properties of Cav3. 2 low-voltage-activated T-type calcium channels"Jpn J Physiol. 53. 165-172 (2003)
Kaku T:“Cav3.2低电压激活的T型钙通道的门控和电导特性”Jpn J Physiol。
DOI: --
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作者: []
通讯作者:
DOI: 10.2170/jjphysiol.53.165
发表时间: 2003-06-01
期刊: JAPANESE JOURNAL OF PHYSIOLOGY
影响因子: --
作者: [Kaku, T, Lee, TS, Ono, K]
通讯作者: Ono, K
6
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    • 批准号:
      21590934
    • 项目类别:
      Grant-in-Aid for Scientific Research (C)
    • 资助金额:
      $2.91万
    • 财政年份:
      2009
    • 负责人:
      ONO Katsushige
    • 依托单位:
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    • 批准号:
      19590823
    • 项目类别:
      Grant-in-Aid for Scientific Research (C)
    • 资助金额:
      $1.41万
    • 财政年份:
      2007
    • 负责人:
      ONO Katsushige
    • 依托单位:
    Research on the development of biopacemaker by use of plnipotent P19CL6 cells.
    • 批准号:
      17590755
    • 项目类别:
      Grant-in-Aid for Scientific Research (C)
    • 资助金额:
      $1.47万
    • 财政年份:
      2005
    • 负责人:
      ONO Katsushige
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    Functional Expression of L-Type Cardiac Calcium Channels in Mammalian Cell in in vivo and in vitro by Use of Adenovirus.
    • 批准号:
      09670049
    • 项目类别:
      Grant-in-Aid for Scientific Research (C)
    • 资助金额:
      $1.09万
    • 财政年份:
      1997
    • 负责人:
      ONO Katsushige
    • 依托单位:
    海外基金