Two-pore channels (TPCs) acts as a hub for excitation-contraction coupling, metabolism and cardiac hypertrophy signalling

IF 4.3 2区 生物学 Q2 CELL BIOLOGY Cell calcium Pub Date : 2023-12-16 DOI:10.1016/j.ceca.2023.102839
Antoine de Zélicourt , Abdallah Fayssoil , Arnaud Mansart , Faouzi Zarrouki , Ahmed Karoui , Jérome Piquereau , Florence Lefebvre , Pascale Gerbaud , Delphine Mika , Mbarka Dakouane-Giudicelli , Erwan Lanchec , Miao Feng , Véronique Leblais , Régis Bobe , Jean-Marie Launay , Antony Galione , Ana Maria Gomez , Sabine de la Porte , José-Manuel Cancela
{"title":"Two-pore channels (TPCs) acts as a hub for excitation-contraction coupling, metabolism and cardiac hypertrophy signalling","authors":"Antoine de Zélicourt ,&nbsp;Abdallah Fayssoil ,&nbsp;Arnaud Mansart ,&nbsp;Faouzi Zarrouki ,&nbsp;Ahmed Karoui ,&nbsp;Jérome Piquereau ,&nbsp;Florence Lefebvre ,&nbsp;Pascale Gerbaud ,&nbsp;Delphine Mika ,&nbsp;Mbarka Dakouane-Giudicelli ,&nbsp;Erwan Lanchec ,&nbsp;Miao Feng ,&nbsp;Véronique Leblais ,&nbsp;Régis Bobe ,&nbsp;Jean-Marie Launay ,&nbsp;Antony Galione ,&nbsp;Ana Maria Gomez ,&nbsp;Sabine de la Porte ,&nbsp;José-Manuel Cancela","doi":"10.1016/j.ceca.2023.102839","DOIUrl":null,"url":null,"abstract":"<div><p>Ca<sup>2+</sup> signaling is essential for cardiac contractility and excitability in heart function and remodeling. Intriguingly, little is known about the role of a new family of ion channels, the endo-lysosomal non-selective cation “two-pore channel” (TPCs) in heart function. Here we have used double TPC knock-out mice for the 1 and 2 isoforms of TPCs (<em>Tpcn1/2<sup>−/−</sup></em>) and evaluated their cardiac function. Doppler-echocardiography unveils altered left ventricular (LV) systolic function associated with a LV relaxation impairment. In cardiomyocytes isolated from <em>Tpcn1/2<sup>−/-</sup></em> mice, we observed a reduction in the contractile function with a decrease in the sarcoplasmic reticulum Ca<sup>2+</sup> content and a reduced expression of various key proteins regulating Ca<sup>2+</sup> stores, such as calsequestrin. We also found that two main regulators of the energy metabolism, AMP-activated protein kinase and mTOR, were down regulated. We found an increase in the expression of TPC1 and TPC2 in a model of transverse aortic constriction (TAC) mice and in chronically isoproterenol infused WT mice. In this last model, adaptive cardiac hypertrophy was reduced by Tpcn1/2 deletion. Here, we propose a central role for TPCs and lysosomes that could act as a hub integrating information from the excitation-contraction coupling mechanisms, cellular energy metabolism and hypertrophy signaling.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"117 ","pages":"Article 102839"},"PeriodicalIF":4.3000,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell calcium","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0143416023001501","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Ca2+ signaling is essential for cardiac contractility and excitability in heart function and remodeling. Intriguingly, little is known about the role of a new family of ion channels, the endo-lysosomal non-selective cation “two-pore channel” (TPCs) in heart function. Here we have used double TPC knock-out mice for the 1 and 2 isoforms of TPCs (Tpcn1/2−/−) and evaluated their cardiac function. Doppler-echocardiography unveils altered left ventricular (LV) systolic function associated with a LV relaxation impairment. In cardiomyocytes isolated from Tpcn1/2−/- mice, we observed a reduction in the contractile function with a decrease in the sarcoplasmic reticulum Ca2+ content and a reduced expression of various key proteins regulating Ca2+ stores, such as calsequestrin. We also found that two main regulators of the energy metabolism, AMP-activated protein kinase and mTOR, were down regulated. We found an increase in the expression of TPC1 and TPC2 in a model of transverse aortic constriction (TAC) mice and in chronically isoproterenol infused WT mice. In this last model, adaptive cardiac hypertrophy was reduced by Tpcn1/2 deletion. Here, we propose a central role for TPCs and lysosomes that could act as a hub integrating information from the excitation-contraction coupling mechanisms, cellular energy metabolism and hypertrophy signaling.

Abstract Image

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
双孔通道(TPC)是兴奋-收缩耦合、新陈代谢和心脏肥大信号的枢纽
在心脏功能和重塑过程中,Ca2+ 信号对心脏收缩力和兴奋性至关重要。耐人寻味的是,人们对一个新的离子通道家族--内溶酶体非选择性阳离子 "双孔通道"(TPCs)--在心脏功能中的作用知之甚少。在这里,我们使用了双TPC基因敲除小鼠(Tpcn1/2-/-),并对其心脏功能进行了评估。多普勒超声心动图显示,左心室收缩功能的改变与左心室松弛功能受损有关。在分离自 Tpcn1/2-/- 小鼠的心肌细胞中,我们观察到收缩功能下降,肌质网 Ca2+ 含量减少,各种调节 Ca2+ 储存的关键蛋白(如钙sequestrin)表达减少。我们还发现,能量代谢的两个主要调节因子--AMP 激活的蛋白激酶和 mTOR--也受到了下调。我们发现,在横纹主动脉缩窄(TAC)小鼠模型和长期注射异丙肾上腺素的 WT 小鼠中,TPC1 和 TPC2 的表达均有所增加。在最后一个模型中,Tpcn1/2 基因缺失会导致适应性心肌肥大减轻。在此,我们提出了 TPCs 和溶酶体的核心作用,它们可以作为一个枢纽,整合来自兴奋-收缩耦合机制、细胞能量代谢和肥大信号的信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Cell calcium
Cell calcium 生物-细胞生物学
CiteScore
8.70
自引率
5.00%
发文量
115
审稿时长
35 days
期刊介绍: Cell Calcium covers the field of calcium metabolism and signalling in living systems, from aspects including inorganic chemistry, physiology, molecular biology and pathology. Topic themes include: Roles of calcium in regulating cellular events such as apoptosis, necrosis and organelle remodelling Influence of calcium regulation in affecting health and disease outcomes
期刊最新文献
NAADP signaling: Master manipulation Electrogenic and non-electrogenic ion antiporters participate in controling membrane potential Commentary on: Li et al.; Ca2+ transients on the T cell surface trigger rapid integrin activation in a timescale of seconds. Nature Communications (2024) Distribution and calcium signaling function of somatostatin receptor subtypes in rat pituitary Calcium signals as regulators of ferroptosis in cancer
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1