Investigation of the physiological functions of anion channels during the differentiation in stem cells.

干细胞分化过程中阴离子通道生理功能的研究。

• 批准号: 20590206
• 负责人: KAWANO Seiko
• 金额: $ 2.91万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590206/
• 关键词: 幹細胞; 分化誘導; イオンチャネル; 心筋細胞; 脂肪細胞; 間葉系幹細胞; クロライドチンネル; 分化; トランスポーター; クロライドチャネル; Ca; ClC family; ES細胞

We investigated the physiological functions of anion channels in mouse embryonic stem cells (mES) and human bone marrow-derived mesenchymal stem cells (hMSCs) during the differentiation to cardiac myocytes or adiposities. Using RT-PCR, the expression of mRNA for ClC-3, ClC-4 and Bestrophin could be detected in both undifferentiated mES cells and hMSCs. In the patch clamp experiments, Ca^<2+> activated outward K^+ currents (I_<KCa>) could be recorded, however, Ca^<2+> activated chloride currents were too small to analyze. Volume sensitive Cl currents were could be recorded in the hypotonic solutions. We concluded that anion channels exist in mES cells and hMSCs and Cl currents coded by ClC-3 have a function in undifferentiated hMSCs. We have demonstrated Cai oscillations in hMSCS previously (2003, 2004, 2005, in Cell Calcium), therefore, we hypothesize that Cai might affect the differentiation processes. When Ca channel blockers were added in the culture medium, adiposeness were inhibited, indicating the contribution of Cai to the differentiating processes from mesenchymal stem cell to adiposities.

我们研究了小鼠胚胎干细胞（mES）和人骨髓间充质干细胞（hMSCs）在向心肌细胞或脂肪细胞分化过程中阴离子通道的生理功能。RT-PCR检测未分化mES细胞和hMSCs中ClC-3、ClC-4和Bestrophin mRNA的表达。在膜片钳实验中，可以记录到Ca^<2+>激活的向外K^+电流（I_<KCa>），但Ca^<2+>激活的氯离子电流太小，无法分析。在低渗溶液中可以记录到体积敏感的Cl电流。我们得出结论，阴离子通道存在于mES细胞和hMSCs中，并且由ClC-3编码的Cl电流在未分化的hMSCs中起作用。我们之前已经证明了Cai在hMSCS中的振荡（2003、2004、2005,Cell Calcium），因此，我们假设Cai可能会影响分化过程。当在培养基中添加Ca通道阻滞剂时，脂肪化受到抑制，表明Cai参与了间充质干细胞向脂肪化的分化过程。

项目成果

BLOCKING KINETICS OF CFTR CHANNEL BY AROMATIC CARBOXYLATE POSITIONAL ISOMERS CHARACTERISED USING A NOVEL AMPLITUDE DISTRIBUTION ANALYSIS METHOD

使用新型振幅分布分析方法表征芳香族羧酸酯位置异构体对 CFTR 通道的阻断动力学

• 发表时间: 2010
• 作者: Ying-Chun Yu;Yoshiro Sohma;Seiko Kawano;et al
• 通讯作者: et al

Blocking kinetics of cftr channel by aromatic carboxylate positional isomers characterised using a novel amplitude distribution analysis method.

使用新型振幅分布分析方法表征芳香族羧酸位置异构体对 cftr 通道的阻断动力学。

• 作者: Ying-Chun Yu、Yoshiro Sohma;Seiko Kawano;et al
• 通讯作者: et al

Synergic effects of β-estradiol and crythromycin on hERG currents

β-雌二醇和红霉素对 hERG 电流的协同作用

• 发表时间: 2011
• 期刊: Journal of Membrane Biology
• 影响因子: 2.4
• 作者: F.Ando;A.Kuruma;S.Kawano
• 通讯作者: S.Kawano

Synergic Effects of β-Estradiol and Erythromycin on hERG Currents

• DOI: 10.1007/s00232-011-9360-z
• 发表时间: 2011-05-01
• 期刊: JOURNAL OF MEMBRANE BIOLOGY
• 影响因子: 2.4
• 作者: Ando, Fumiaki;Kuruma, Akinori;Kawano, Seiko
• 通讯作者: Kawano, Seiko