Complexity of the regulation of L-type calcium channels

L 型钙通道调节的复杂性

• 批准号: 15590188
• 负责人: KAMEYAMA Masaki
• 金额: $ 2.11万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590188/
• 关键词: Ca channels; cardiac myocyte; patch clamp; calmodulin; calpastatin; rundown

L-type Ca channels in cardiac tissues are regulated by intracellular factors, such as calmodulin(CaM), CaM kinase II(CaMKII) and calpastatin. In this study, following points are clarified.1.Domain L of calpatatin is known to activate the Ca channels. In this study, we found that a fragment peptide with amino acid number 54-64 has similar effect, suggesting that this region might be an active site for the interaction with the channel.2.CaM is known to activate rundown channels. In this study, we found that a mutant CaM lacking all four Ca-binding sites can also activate the rundown channels, suggesting that apoCaM interacts with the channel.3.CaMKII inhibitors reduce basal activity of the Ca channels, suggesting a certain role of CaMKII in the basal activity of the channel.4.Inhibitors of CaM suppressed the facilitation and inactivation during Ca overload, while inhibitors of CaMKII had minimal effect. This suggest that CaM plays an major role in the facilitation and inactivation induced by a rise of intracellular Ca.

心肌组织中的L型钙通道受细胞内钙调素(CaM)、钙调蛋白激酶II(CaMKII)和钙调蛋白(Calastatin)等细胞因子的调节。在本研究中，明确了以下几点：1.已知Calpatatin的L结构域可以激活钙通道。在本研究中，我们发现一个氨基酸序号为54-的片段具有类似的作用，提示该区域可能是与通道相互作用的活性部位。2.已知CaM激活衰减性通道。在本研究中，我们发现缺失所有四个钙结合位点的突变体CaM也可以激活通道，提示apoCaM与通道相互作用。3.CaMKII抑制剂降低钙通道的基础活性，提示CaMKII在通道的基础活动中起一定作用。4.CaM的抑制剂抑制钙超载时的促进和失活，而CaMKII的抑制剂作用很小。这表明CaM在细胞内钙升高引起的易化和失活过程中起主要作用。

项目成果

Mechanism of action of voltage-gated K^+ channel antibodies in acquired neuromyotonia.

电压门控K + 通道抗体在获得性神经肌强直中的作用机制。

• 发表时间: 2004
• 期刊: Ann Neurol 56
• 作者: Tomimitsu H;Arimura K;Nagado T;Watanabe O;Otsuka R;Kurono A;Sonoda Y;Osame M;Kameyama M.
• 通讯作者: Kameyama M.

Kameyama M: "Mechanisms underling basal activity of L-tipe Ca^<2+> channels"Japanese Journal of Physiology. 53. s49-s49 (2003)

Kameyama M：“L-tipe Ca^<2>通道基础活性的机制”日本生理学杂志。

Regulation of L-type Ca^<2+> channels in the heart : Overivew of recent advancements.

心脏中 L 型 Ca^<2> 通道的调节：最新进展概述。

• 发表时间: 2003
• 期刊: J Mol Cell Biochem 253
• 作者: Yamaoka K;Kameyama M
• 通讯作者: Kameyama M

Calmodulin reverses rundown of L-type Ca(2+) channels in guinea pig ventricular myocytes.

• DOI: 10.1152/ajpcell.00105.2004
• 发表时间: 2004-12
• 期刊: American journal of physiology. Cell physiology
• 作者: Jianjun Xu;L. Hao;A. Kameyama;M. Kameyama

IgM antibody suppressed voltage-gated potassium channels in acquired meuromyotonia.

IgM 抗体抑制获得性神经肌强直中的电压门控钾通道。

• 发表时间: 2005
• 期刊: Muscle Nerve (in press)
• 作者: Kurono A;Arimura K;Watanabe O;Tomimitsu H;Nagado T;Sonoda Y;Kameyama M;Ng A;Osame M.
• 通讯作者: Osame M.