Study with knockout mice on the activation mechanisms of the capacitative Ca^<2+> entry channel existing in the cardiac myocyte

敲除小鼠心肌细胞电容性Ca^2进入通道激活机制研究

• 批准号: 14570051
• 负责人: UEHARA Akira
• 金额: $ 2.18万
• 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: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570051/
• 关键词: Heart; Calcium; Sarcoplasmic reticulum

We have explored whether the capacitative Ca^<2+> entry (CCE) mechanisms exists in heart muscle with a fluorescent [Ca]_i measurement technique. By the reintroduction of external Ca^<2+> after the depletion of Ca^<2+> stored in sarcoplasmic reticulum (SR) using Ca^<2+> pump inhibitors or ryanodine receptor (RyR) activators, a huge steady rise in cytoplasmic Ca^<2+> concentration at both tissue and single cell levels was evoked even in the presence of L-type Ca^<2+> channel antagonists. Such a CCE activity was sensitive to Zinc but insensitive to the other many cation blockers in possible molecular entities of CCE channels of TRP and Icrac channel families. Here we could thus first demonstrate from embryonic to neonatal stages at least that the PL membrane of the cardiac myocyte is endowed with a store-operated Ca^<2+> entry pathway. Cardiac SR could be refilled with Ca^<2+> via the CCE pathway and reset as a functional regulator of the cytoplasmic Ca^<2+> concentration to induce the multiple Ca^<2+> dependent cellular function, whenever the stored Ca^<2+> in the SR lumen is consumed and subsequently depleted during ontogenetic developing stages or under some physiological and pathophysiological conditions.

我们用荧光[Ca]_i测量技术研究了心肌中是否存在电容性钙内流(CCE)机制。用钙泵抑制剂或Ryanodine受体(RyR)激动剂耗尽储存在肌浆网(SR)中的钙离子后，通过重新引入外部钙离子，即使在L型钙通道拮抗剂存在的情况下，细胞内钙离子浓度也能在组织和单个细胞水平上显著增加。在Trp和Icrc通道家族CCE通道的可能分子实体中，这种CCE活性对锌敏感，而对其他许多阳离子阻滞剂不敏感。在这里，我们可以首先证明，至少从胚胎到新生儿阶段，心肌细胞的磷脂膜被赋予了一条钙库操作的钙离子进入途径。心脏肌浆网可通过CCE途径重新充盈，并作为细胞质内钙离子浓度的功能调节器，在个体发育阶段或某些生理和病理生理条件下，一旦储存在肌浆网中的钙被消耗和耗尽，就可以诱导多种钙依赖的细胞功能。

项目成果

Uehara, A., Yasukochi, M., Imanaga, I., Nishi, M., Takeshima, H.: "Store-operated Ca^<2+> entry uncoupled with ryanodine receptor and junctional membrane complex in heart muscle"Cell Calcium. 31. 89-96 (2002)

Uehara, A.、Yasukochi, M.、Imanaga, I.、Nishi, M.、Takeshima, H.：“与心肌中兰尼碱受体和交界膜复合体解偶联的存储操作的 Ca^2 进入”细胞钙。

Uehara, A.et al.: "Store-operated Ca^<2+> entry uncoupled with ryanodine receptor and junctional membrane complex in heart muscle"Cell Calcium. 31. 89-96 (2002)

Uehara，A.等人：“与兰尼碱受体和心肌中的连接膜复合体解偶联的存储操作的Ca ^ 2 进入”细胞钙。