Intracellular regulation of Ca^<2+> release from cardiac sarcoplasmic reticulum.

心脏肌浆网Ca ^ 2 释放的细胞内调节。

• 批准号: 05670040
• 负责人: KAWANO Seiko
• 金额: $ 1.54万
• 依托单位: Tokyo Medical and Dental University, Medical Research Institute.
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670040/
• 关键词: Sarcoplasmic Reticulum; Ryanodine Receptor; Ca^<2+>; Cl-channel; Cardiac Myocyte; Signal Transduction; リアノジン受容体; 細胞内Ca^<2+>; クロライドチャネル; 筋小胞体; Mg^<2+>; イオンチャネル; カルモジュリン; カルシュウム

I have investigated the regulatory mechanism of ion channels in cardiac sarcoplasmic reticulum by recording single channel currents.(1) I found that Cl-channel existed in cardiac sarcoplasmic reticulum (SR) and that this channel was activated by cyclic AMP-dependent phosphorylation and was inhibited by Ca^<2+>/calmodulin complex. These are new evidences of intracellular channel regulations. I published the paper about these evidences (Circulation Research, 1993). (2) Ryanodine receptor Ca^<2+> release channel (RyR) in SR playd the important role for Ca^<2+> supply in the cells. We examined the regulatory mechanisms of RyR by recordingsingle channel activities and found that these channel openings were enhanced by scorpion toxin, which might be the new type of activator for ryanodine receptor. Ca^<2+> antagonist, verapamil, blocked ryanodine receptor channel openings directly to reduce the contraction of the heart. I showed the detail regulatory mechanisms of Ca^<2+> release from SR by Mg^<2+>.(2) Intracellular Ca^<2+> is supplied from SR and plays many important roles for cell functions. I found that cardiac sarcolemma had Ca^<2+> -activated C1-channel and examined the detail activation mechanisms of this channel by intracellular Ca^<2+>. This paper is now in press of Journal of Physiology in London. I need to study the further regulatory mechanisms of this Cl-channel.

我通过记录单通道电流研究了心肌肌浆网离子通道的调节机制。(1)我发现心肌肌浆网（SR）中存在Cl-通道，该通道被环腺苷酸依赖性磷酸化激活，并被Ca^2+/钙调素复合物抑制。这些都是细胞内通道调节的新证据。我发表了关于这些证据的论文（循环研究，1993）。(2)SR上Ryanodine受体Ca^2+释放通道（RyR）在细胞内Ca^2+供应中起重要作用。我们通过记录RyR的单通道活动研究了RyR的调节机制，发现这些通道的开放被蝎毒素增强，蝎毒素可能是Ryanodine受体的新型激活剂。Ca^2+拮抗剂维拉帕米可直接阻断兰尼碱受体通道的开放，从而减少心脏的收缩。本文详细阐述了Mg^<2 +>对SR释放Ca^<2 +>的调控机制. (2)细胞内Ca^<2+>由SR提供，并在细胞功能中起着许多重要作用。我发现心肌细胞膜上存在Ca^<2+>激活的C1-通道，并研究了细胞内Ca^<2+>激活该通道的详细机制。这篇论文正在伦敦的《生理学杂志》上付印。我需要进一步研究这个氯离子通道的调节机制。

项目成果

川野誠子: "図説病態内科講座.循環器病-1" 高久史麿.メジカルビュー社, 12 (1993)

Seiko Kawano：“病理内科图解课程。心血管疾病-1” Fumaro Takahisa 出版，12（1993）。

Seiko Kawano, Yoshiyuki Hirayama, & Masayasu Hiraoka: "Activation Mechanism of [Ca^<2+>] _i-sensitive Transient Outward Current in Rabbit Ventricular Myocytes." Journal of Physiology (London). (in press). (1995)

河野圣子、平山由之、

Seiko Kawano: "Activation Mechanism of[Ca^<2+>]_i-sensitive Transient Outward Current in Rabbit Ventricular Myocytes." Journal of Physiology(London). (in press,). (1995)

Seiko Kawano：“兔心室肌细胞中[Ca^<2>]_i敏感瞬态外向电流的激活机制”。

川野誠子: "イオンチャネルセレプターと細胞情報" 三品昌美.御子柴克彦.羊土社, 8 (1994)

Seiko Kawano：“离子通道受体和细胞信息”Masami Mishina，Yodosha，8 (1994)。

Seiko Kawano, & Masayasu Hiraoka: "Protein Kinase A-activated Chloride Channel is inhibited by the Ca^<2+>-calmodulin Complex in Cardiac Sarcoplasmic Reticulum" Circulation Research. 73. 751-757 (1993)

河野圣子,