Modulatory mechanisms of cardiac ion channels.

心脏离子通道的调节机制。

• 批准号: 07044233
• 负责人: HIRAOKA Masayasu
• 金额: $ 5.38万
• 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 international Scientific Research
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07044233/
• 关键词: protein phosphorylation; L-type Ca^<2+> channel; ATP-sensitive; K^+ channel; HERG K^+ channel; Ca^<2+> -activated Cl^- -channel; Ryanodine receptor channel; α受容体; cGMP; Ca活性化Clチャネル

The collaboration with Professor H.A.Fozzard has made a great advance in the technical achievements of the expressed channels functions and structural confirmation. We also acquired the clones of ATP-sensitive K^+ channel. Now, we are ready to express these K^+ channels and functional modulation of HERG K channel by tyrosin phosphorylation is under investigation. Furthermore, mutation of HERG K^+ channels is one of etiological factors for long QT syndrome. Therefore, we started to examine functional abnormality of the mutated channels. The joint research with Professor H.C.Hartzell has made a great advance for the purification of ryanodine receptor channel proteins, which enables us to study their function with much higher success rate. Modulation of Ca^<2+> -activated Cl^- -channel and L-type Ca^<2+> channel by protein phosphorylation and phosphatases is now studied with refined technique and new information owing to the fruits of this joint research.

与H.A.Fozzard教授的合作，在表达经络功能和结构确认的技术成果上取得了很大的进步。我们还获得了atp敏感的K^+通道的克隆。现在，我们准备表达这些K^+通道，并且正在研究酪氨酸磷酸化对HERG K通道的功能调节。此外，HERG K^+通道突变是长QT综合征的病因之一。因此，我们开始研究突变通道的功能异常。与H.C.Hartzell教授的联合研究在ryanodine受体通道蛋白的纯化方面取得了很大的进展，使我们能够以更高的成功率研究其功能。通过蛋白磷酸化和磷酸酶对Ca^<2+> -激活的Cl^-通道和l型Ca^<2+>通道的调节，现在通过精细化的技术和新的信息进行了研究。

项目成果

Hirano Y,Yoshinaga T,Niidome T,Katayama K,Hiraoka M.: "Modulation by dihydropyridine and protein kinases of the recombinant cardiac L-type Ca channel with multiple unitary current amplitudes." Receptors and Channels. 4. 93-104 (1996)

Hirano Y、Yoshinaga T、Niidome T、Katayama K、Hiraoka M.：“二氢吡啶和蛋白激酶对重组心脏 L 型 Ca 通道的调节，具有多个单一电流幅度。”

Hiraoka M.: "Pathophysiological functions of ATP-sensitive K^+ channels in myocardial ischemia." Jpn.Heart J.(in press). (1997)

Hiraoka M.：“ATP 敏感 K^ 通道在心肌缺血中的病理生理功能。”

Hiraoka M,Furukawa T,Sawanobori T,Yamane T.: Springer-Verlag, Tokyo. Regulation of rundown and reactivation of cardiac ATP-sensitive K^+ channels. In "Molecular and Cellular Mechanisms of Cardiovascular Regulations"., 83-91 (1996)

Hiraoka M、Furukawa T、Sawanobori T、Yamane T.：Springer-Verlag，东京。

Zhang S.,Hirano Y.& Hiraoka M.: "Arginine-vasopressin induced potentiation of unitary l-type calcium channel current in guinea-pig ventricular myocyte" Circulation Research. 76. 592-595 (1995)

张S.,平野Y.

Hiraoka M,Furukawa T,Sawanobori T.& Yamane T.: "Regulation of cardiac delayed rectifier K^+ channels and ATP-sensitive K^+ channels by intracellular factors.In Potassium Channels in Normal and Pathological Conditions." Leuven University Press, 103-117 (19

平冈 M、古川 T、泽诺堀 T.