Electrophysiologicalestudy on the cardiac ryanodine receptor operating the Ca-induced Ca-release mechanisms.

心脏兰尼碱受体操作 Ca 诱导的 Ca 释放机制的电生理学研究。

• 批准号: 12670050
• 负责人: AKIRA Uehara
• 金额: $ 1.92万
• 依托单位: Fukuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670050/
• 关键词: Heart; Sarcoplasmic reticulum; Ryanodine receptor; Calcium

Performing the two-year project on "Electrophysiological study on the cardiac ryanodine receptor (RyR) operating the Ca-induced Ca-release mechanisms", we obtained the following results. The single-channel activity from the cardiac RyR was reconstituted into planar lipid bilayers.(1) We explored a modulation mechanism of the channel activity of the RyR via a phosphorylation. The RyR was activated by the protein kinase A subunit. The phosphorylated RyR channels open/close more frequently, stay open longer, stay closed for shorter periods. It was improved that the activation is ascribable to the decrease in sensitivity to the cytosolic blocking ligarid of Mg ion. A paper on this work was recently accepted by Pflugers Archiv.(2) We investigated another modulation mechanism of the channel activity of the RyR by the pathophysiological metabolytes from membrane lipids such as sphingolipids. Although this substance is lipid, it is likely to bind to the specific cytoplasmic site of the channel molecule and to block the channel activity. A paper on this work was already submitted to some journal.(3) We also analysed the inactivation mechanism of the real current of the RyR to inhibit the Ca-induced Ca-release. We are now preparing a paper on this work.Thus, some novel regulation mechanisms by cytoplasmic metabolites of the cardiac myocytes on RyR which exerts a central role of the Ca-induced Ca release have been elucidated.

我们进行了为期两年的“心脏兰尼碱受体（RyR）操作钙诱导钙释放机制的电生理学研究”项目，获得了以下结果。心脏RyR的单通道活性被重构为平面脂质双层。(1)我们探索了通过磷酸化调节RyR通道活性的机制。 RyR 被蛋白激酶 A 亚基激活。磷酸化的 RyR 通道打开/关闭更频繁，打开时间更长，关闭时间更短。改进了激活是由于对镁离子胞质封闭配体的敏感性降低所致。关于这项工作的论文最近被 Pflugers Archive 接受。(2) 我们研究了来自膜脂（如鞘脂）的病理生理代谢产物对 RyR 通道活性的另一种调节机制。尽管这种物质是脂质，但它很可能与通道分子的特定细胞质位点结合并阻断通道活性。有关这项工作的论文已经提交给一些期刊。(3)我们还分析了RyR真实电流抑制Ca诱导的Ca释放的​​失活机制。我们现在正在准备一篇关于这项工作的论文。因此，心肌细胞的细胞质代谢物对 RyR 的一些新的调节机制已经被阐明，RyR 在 Ca 诱导的 Ca 释放中发挥着核心作用。

项目成果

Uehara, A. et al.: "Gating kinetics and ligand sensitivity modified by phosphorylation of cardiac ryanodine receptors"Pflugers Arch.Eur.J.Physiol. (in press Accepted on Jan.3,2002). (2002)

Uehara, A. 等人：“通过心脏兰尼碱受体磷酸化修饰的门控动力学和配体敏感性”Pflugers Arch.Eur.J.Physiol。

Uehara A., et al.: "Gating kinetics and ligand sensitivity modified by phosphorylation of cardiac ryanodine receptors"Pflugers Arch. Eur. J. Physiol.. (in press), Accepted on Jan. 3. (2002)

Uehara A.等人：“通过心脏兰尼碱受体磷酸化修饰的门控动力学和配体敏感性”Pflugers Arch。

Uehara, A. et al.: "Gating kinetics and ligand sensitivity modified by phosphorylation of cardiac ryanodine receptors"Pflugers Arch. Eur. J. Physiol.. (in press, Accepted on Jan. 3,2002). (2002)

Uehara, A. 等人：“通过心脏兰尼碱受体磷酸化修饰的门控动力学和配体敏感性”Pflugers Arch。