The investigation of altered Ca2+ handling by the selective modulation of Ca2+ uptake rate of sarcoplasmic reticulum

通过选择性调节肌浆网 Ca2 摄取率改变 Ca2 处理的研究

• 批准号: 23790255
• 负责人: MORIMOTO Satoshi
• 金额: $ 2.08万
• 依托单位: Jikei University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790255/
• 关键词: 細胞内Ca2+動態; 心筋筋小胞体; ATP依存性筋小胞体Ca2+ポンプ; 国際情報交換; 国際情報交流

We investigated the role of the alteration of sarcoplasmic reticulum (SR) which is known to be a cause of cardiac dysfunction in failing heart. We used saponin-treated thin trabeculae obtained from mice hearts with overexpression of SR-Ca2+ ATPase (SERCA-TG) and sarcolipin (SLN-TG), respectively. Ca2+ uptake rate was faster in SERCA-TG and slower in SLN-TG. Maximal Ca2+ content, Ca2+ induced Ca2+ release and Ca2+ leak were not altered in SERCA-TG and SLN-TG. In the papillary muscle experiment using Ca2+ sensitive photoprotein aequorin, peak tension and peak amplitude of Ca2+ transient were increased in SERCA-TG and decreased in SLN-TG. Relaxation time of tension and decline of Ca2+ transient were accelerated in SERCA-TG and prolonged in SLN-TG. Thus, we concluded that selective modulation of Ca2+ uptake into SR influenced the amplitude and time course of Ca2+ transient and tension, however, it did not influence maximal Ca2+ content, Ca2+ induced Ca2+ release and Ca2+ leak of SR.

我们研究了肌浆网（SR）的改变的作用，这是已知的心力衰竭的心功能不全的原因。我们使用从SR-Ca ~（2+）ATPase（SERCA-TG）和sarcolipin（SLN-TG）过表达的小鼠心脏获得的皂苷处理的薄梁。SERCA-TG的Ca ~（2+）摄取速率快于SLN-TG。SERCA-TG和SLN-TG的最大Ca ~（2+）含量、Ca ~（2+）诱导的Ca ~（2+）释放和Ca ~（2+）渗漏均未发生改变。在使用Ca ~（2+）光敏蛋白aequorin的乳头肌实验中，SERCA-TG的Ca ~（2+）瞬变峰张力和峰幅度增加，SLN-TG的Ca ~（2+）瞬变峰张力和峰幅度降低。SERCA-TG组张力松弛时间和钙瞬变下降时间明显加快，SLN-TG组延长。因此，我们认为，选择性调节SR的Ca ~（2+）摄取可以影响SR的Ca ~（2+）瞬变和张力的幅度和时程，但不影响SR的最大Ca ~（2+）含量、Ca ~（2+）诱导的Ca ~（2+）释放和Ca ~（2+）渗漏。

项目成果

Selective modulation of SERCA did not affect the Ca2+ leak from the sarcoplasmic reticulum in transgenic mouse models

SERCA 的选择性调节不影响转基因小鼠模型中肌浆网的 Ca2 泄漏

• 发表时间: 2014
• 作者: Morimoto S;Hongo K;Kusakari Y;Komukai K;Kawai M;Kurihara S;Yoshimura M
• 通讯作者: Yoshimura M

Modulation of Ca2+ uptake by changing of SERCA activity in mouse myocardium did not alter Ca2+ leak from sarcoplasmic reticulum in physiological condition

通过改变小鼠心肌 SERCA 活性来调节 Ca2 摄取，不会改变生理条件下肌浆网的 Ca2 渗漏

• 发表时间: 2013
• 作者: Morimoto S;Kusakari Y;O-Uchi J;Komukai K;Kawai M;Yoshimura M;Hongo K;Kurihara S
• 通讯作者: Kurihara S

SERCAもしくはsarcolipinの過剰発現はマウス心筋におけるCa2+誘発性Ca2+放出とCa2+リークに影響を与えない

SERCA 或肌磷脂的过表达不影响小鼠心肌中 Ca2+ 诱导的 Ca2+ 释放和 Ca2+ 渗漏。

• 发表时间: 2014
• 作者: Kitagawa S;Kato T;他、Chapter V. ed. E.M. Lashinski;森本智,本郷賢一,草刈洋一郎,小武海公明,川井真,吉村道博,栗原敏
• 通讯作者: 森本智,本郷賢一,草刈洋一郎,小武海公明,川井真,吉村道博,栗原敏