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区域差异在钙离子信号转导和横管在成年羊左心房。

Regional Differences in Ca Signaling and Transverse-Tubules across Left Atrium from Adult Sheep.

机构信息

INSERM U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Université de Bordeaux, 33000 Bordeaux, France.

IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, 33000 Bordeaux, France.

出版信息

Int J Mol Sci. 2023 Jan 25;24(3):2347. doi: 10.3390/ijms24032347.

DOI:10.3390/ijms24032347
PMID:36768669
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9916916/
Abstract

Cardiac excitation-contraction coupling can be different between regions of the heart. Little is known at the atria level, specifically in different regions of the left atrium. This is important given the role of cardiac myocytes from the pulmonary vein sleeves, which are responsible for ectopic activity during atrial fibrillation. In this study, we present a new method to isolate atrial cardiac myocytes from four different regions of the left atrium of a large animal model, sheep, highly relevant to humans. Using collagenase/protease we obtained calcium-tolerant atrial cardiac myocytes from the epicardium, endocardium, free wall and pulmonary vein regions. Calcium transients were slower (time to peak and time to decay) in free wall and pulmonary vein myocytes compared to the epicardium and endocardium. This is associated with lower t-tubule density. Overall, these results suggest regional differences in calcium transient and t-tubule density across left atria, which may play a major role in the genesis of atrial fibrillation.

摘要

心脏的兴奋-收缩偶联在心脏的不同区域可能不同。在心房水平,特别是在左心房的不同区域,知之甚少。鉴于肺静脉袖套中的心肌细胞在心房颤动期间发生异位活动的作用,这一点非常重要。在这项研究中,我们提出了一种从绵羊等大型动物模型的左心房四个不同区域分离心房心肌细胞的新方法,与人类高度相关。使用胶原酶/蛋白酶,我们从心外膜、心内膜、游离壁和肺静脉区域获得了钙耐受的心房心肌细胞。与心外膜和心内膜相比,游离壁和肺静脉心肌细胞的钙瞬变较慢(达峰时间和衰减时间)。这与较低的 t 小管密度有关。总的来说,这些结果表明左心房钙瞬变和 t 小管密度存在区域性差异,这可能在心房颤动的发生中起主要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2fb/9916916/2a726b961d1f/ijms-24-02347-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2fb/9916916/3042be877f2c/ijms-24-02347-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2fb/9916916/c308b1c662dc/ijms-24-02347-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2fb/9916916/2a726b961d1f/ijms-24-02347-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2fb/9916916/3042be877f2c/ijms-24-02347-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2fb/9916916/c308b1c662dc/ijms-24-02347-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2fb/9916916/2a726b961d1f/ijms-24-02347-g003.jpg

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本文引用的文献

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Region-specific distribution of transversal-axial tubule system organization underlies heterogeneity of calcium dynamics in the right atrium.跨轴向管系统组织的区域特异性分布是右心房钙动力学异质性的基础。
Am J Physiol Heart Circ Physiol. 2022 Feb 1;322(2):H269-H284. doi: 10.1152/ajpheart.00381.2021. Epub 2021 Dec 24.
2
The Physiology and Pathophysiology of T-Tubules in the Heart.心脏中横管的生理学与病理生理学
Front Physiol. 2021 Sep 9;12:718404. doi: 10.3389/fphys.2021.718404. eCollection 2021.
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Animal Models of Atrial Fibrillation.
房颤动物模型。
Circ Res. 2020 Jun 19;127(1):91-110. doi: 10.1161/CIRCRESAHA.120.316366. Epub 2020 Jun 18.
4
Structural heterogeneity of the rat pulmonary vein myocardium: consequences on intracellular calcium dynamics and arrhythmogenic potential.大鼠肺静脉心肌的结构异质性:对细胞内钙动力学和致心律失常潜能的影响。
Sci Rep. 2018 Feb 19;8(1):3244. doi: 10.1038/s41598-018-21671-9.
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Calcium Signaling and Cardiac Arrhythmias.钙信号与心律失常
Circ Res. 2017 Jun 9;120(12):1969-1993. doi: 10.1161/CIRCRESAHA.117.310083.
6
Cardiac expression of ryanodine receptor subtype 3; a strategic component in the intracellular Ca release system of Purkinje fibers in large mammalian heart.兰尼碱受体亚型3的心脏表达;大型哺乳动物心脏浦肯野纤维细胞内钙释放系统的一个关键组成部分。
J Mol Cell Cardiol. 2017 Mar;104:31-42. doi: 10.1016/j.yjmcc.2017.01.011. Epub 2017 Jan 20.
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Heart Rhythm. 2017 Feb;14(2):273-281. doi: 10.1016/j.hrthm.2016.09.022. Epub 2016 Sep 23.
8
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Heterogeneity of T-Tubules in Pig Hearts.猪心脏中横小管的异质性。
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Cardiovasc Res. 2015 Dec 1;108(3):387-98. doi: 10.1093/cvr/cvv231. Epub 2015 Oct 21.