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钙处理先于心脏分化以启动第一次心跳。

Calcium handling precedes cardiac differentiation to initiate the first heartbeat.

作者信息

Tyser Richard Cv, Miranda Antonio Ma, Chen Chiann-Mun, Davidson Sean M, Srinivas Shankar, Riley Paul R

机构信息

Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.

The Hatter Cardiovascular Institute, University College London and Medical School, London, United Kingdom.

出版信息

Elife. 2016 Oct 11;5:e17113. doi: 10.7554/eLife.17113.

DOI:10.7554/eLife.17113
PMID:27725084
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5059139/
Abstract

The mammalian heartbeat is thought to begin just prior to the linear heart tube stage of development. How the initial contractions are established and the downstream consequences of the earliest contractile function on cardiac differentiation and morphogenesis have not been described. Using high-resolution live imaging of mouse embryos, we observed randomly distributed spontaneous asynchronous Ca-oscillations (SACOs) in the forming cardiac crescent (stage E7.75) prior to overt beating. Nascent contraction initiated at around E8.0 and was associated with sarcomeric assembly and rapid Ca transients, underpinned by sequential expression of the Na-Ca exchanger (NCX1) and L-type Ca channel (LTCC). Pharmacological inhibition of NCX1 and LTCC revealed rapid development of Ca handling in the early heart and an essential early role for NCX1 in establishing SACOs through to the initiation of beating. NCX1 blockade impacted on CaMKII signalling to down-regulate cardiac gene expression, leading to impaired differentiation and failed crescent maturation.

摘要

哺乳动物的心跳被认为在发育的线性心管阶段之前就开始了。最初的收缩是如何建立的，以及最早的收缩功能对心脏分化和形态发生的下游影响尚未得到描述。通过对小鼠胚胎进行高分辨率实时成像，我们在明显跳动之前的形成中的心脏新月区（E7.75期）观察到随机分布的自发异步钙振荡（SACOs）。新生收缩在大约E8.0开始，并与肌节组装和快速钙瞬变相关，这由钠钙交换体（NCX1）和L型钙通道（LTCC）的顺序表达所支撑。对NCX1和LTCC的药理学抑制揭示了早期心脏中钙处理的快速发展，以及NCX1在建立SACOs直至跳动开始过程中的重要早期作用。NCX1阻断影响钙调蛋白激酶II信号传导，从而下调心脏基因表达，导致分化受损和新月区成熟失败。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beff/5059139/862ea3589881/elife-17113-fig5-figsupp3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beff/5059139/0ea249072d86/elife-17113-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beff/5059139/d88f32c8b035/elife-17113-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beff/5059139/047653789a1d/elife-17113-fig5-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beff/5059139/862ea3589881/elife-17113-fig5-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beff/5059139/62ca0684284f/elife-17113-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beff/5059139/b15da465a07a/elife-17113-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beff/5059139/d8e850bb3ca9/elife-17113-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beff/5059139/408c9c2f9ecd/elife-17113-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beff/5059139/aef0d9ef7c1b/elife-17113-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beff/5059139/2e689af9e09f/elife-17113-fig2-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beff/5059139/8a97eb28179b/elife-17113-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beff/5059139/a4e8b1e0a039/elife-17113-fig3-figsupp1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beff/5059139/0ebf578a6670/elife-17113-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beff/5059139/b49e787266dd/elife-17113-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beff/5059139/0ea249072d86/elife-17113-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beff/5059139/d88f32c8b035/elife-17113-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beff/5059139/047653789a1d/elife-17113-fig5-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beff/5059139/862ea3589881/elife-17113-fig5-figsupp3.jpg

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