Tyser, RCV;
Miranda, AMA;
Chen, C-M;
Davidson, SM;
Srinivas, S;
Riley, PR;
(2016)
Calcium handling precedes cardiac differentiation to initiate the first heartbeat.
eLIFE
, 5
, Article e17113. 10.7554/eLife.17113.
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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 Ca2+-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 Ca2+ transients, underpinned by sequential expression of the Na+-Ca2+ exchanger (NCX1) and L-type Ca2+ channel (LTCC). Pharmacological inhibition of NCX1 and LTCC revealed rapid development of Ca2+ 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.
| Type: | Article |
|---|---|
| Title: | Calcium handling precedes cardiac differentiation to initiate the first heartbeat |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.7554/eLife.17113 |
| Publisher version: | http://doi.org/10.7554/eLife.17113 |
| Language: | English |
| Additional information: | © Copyright Tyser et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Biology, Life Sciences & Biomedicine - Other Topics, INTRACELLULAR CA2+ OSCILLATIONS, EMBRYONIC MOUSE HEART, PROTEIN-KINASE-II, NA+/CA2+ EXCHANGER, SMOOTH-MUSCLE, MYOCARDIAL-CELLS, MAMMALIAN HEART, NA/CA EXCHANGE, STEM-CELLS, HYPERTROPHY |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1522179 |
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