Investigation on possible link between Ist and CaV1.3 RNA editing

Ist 和 CaV1.3 RNA 编辑之间可能联系的调查

• 批准号: 23590258
• 负责人: TOYODA Futoshi
• 金额: $ 3.41万
• 依托单位: Shiga University of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-23590258/
• 关键词: 心臓; ペースメーカー; 洞房結節; イオンチャネル; 洞房結節細胞; ペースメーカー機序; 膜電流; 国際情報交換（フランス）; 心臓ペースメーカー

The sustained inward Na+ current (Ist) in sinoatrial node (SAN) pacemaker cells has been suggested to contribute to the pacemaker activity, although unknown molecular correlates of this current limits the understanding of its significance in the pacemaker activity. The purpose of this study was 1) to examine the relationship between L-type Ca2+ channel CaV1.3 subunit and Ist in their functional expression levels, and 2) to identify the RNA editing-mediated CaV1.3 variants. The density of Ist was positively correlated with the magnitude of L-type Ca2+ current (ICa,L). In knock-out mice with disruption of CaV1.3, ICa,L was significantly reduced, which was accompanied by a complete loss of Ist. Comprehensive analysis of CaV1.3 transcripts using the second generation sequencer revealed the presence of rare variants with residue changes in the Ca2+ selectivity filter. These findings suggest that Ist is mediated by CaV1.3 variants Ist in SAN pacemaker cells.

窦房结（SAN）起搏细胞的持续性内向Na+电流（Ist）被认为与起搏活动有关，但该电流的分子相关性尚不清楚，限制了对其在起搏活动中意义的理解。本研究的目的是：1）检测L型钙通道CaV1.3亚基与Ist在功能表达水平上的关系; 2）鉴定RNA编辑介导的CaV1.3变异体。Ist的密度与L型钙电流（伊卡，L）的大小呈正相关。在CaV1.3基因敲除小鼠中，伊卡，L显著降低，并伴随着Ist的完全丧失。使用第二代测序仪对CaV1.3转录本进行的综合分析揭示了在Ca 2+选择性过滤器中存在具有残基变化的罕见变体。这些结果表明，在SAN起搏细胞中，Ist是由CaV1.3变体Ist介导的。

项目成果

CaV1.3 α1D subunit is involved in the sustained inward Na+ current in mouse SAN cells

CaV1.3 α1D 亚基参与小鼠 SAN 细胞中持续的内向 Na+ 电流

• 发表时间: 2014
• 作者: Toyoda F;Mesirca P;Dubel S;Ding WG;Striessnig J;Mangoni ME;Matsuura H
• 通讯作者: Matsuura H

The G-protein-gated K+ channel, IKACh, is required for regulation of pacemaker activity and recovery of resting heart rate after sympathetic stimulation.

• DOI: 10.1085/jgp.201310996
• 发表时间: 2013-08
• 期刊: The Journal of general physiology
• 作者: Mesirca P;Marger L;Toyoda F;Rizzetto R;Audoubert M;Dubel S;Torrente AG;Difrancesco ML;Muller JC;Leoni AL;Couette B;Nargeot J;Clapham DE;Wickman K;Mangoni ME
• 通讯作者: Mangoni ME

Improved functional expression of human cardiac kv1.5 channels and trafficking-defective mutants by low temperature treatment.

• DOI: 10.1371/journal.pone.0092923
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Ding WG;Xie Y;Toyoda F;Matsuura H
• 通讯作者: Matsuura H

The COX-2 selective blocker etodolac inhibits TNFα-induced apoptosis in isolated rabbit articular chondrocytes.

• DOI: 10.3390/ijms141019705
• 发表时间: 2013-09-30
• 期刊: International journal of molecular sciences
• 影响因子: 5.6
• 作者: Kumagai K;Kubo M;Imai S;Toyoda F;Maeda T;Okumura N;Matsuura H;Matsusue Y
• 通讯作者: Matsusue Y

Cellular heterogeneity of the sustained inward Na+ current in guinea-pig sinoatrial node.

豚鼠窦房结持续内向Na电流的细胞异质性。

• 发表时间: 2012
• 作者: Toyoda F;Ding WG;Matsuura H.
• 通讯作者: Matsuura H.