Characterising the initiation of coordinated calcium transients in the developing heart

Oxford

£27,617

2015

Our work has looked at when during embryogenesis the forming heart can be said to start ‘beating’. We found that sarcomeric arrangement of cardiomyocyte contractile molecules is present early in the cardiac crescent, at stages when we can visually detect contractile activity. Oscillations of cytosolic calcium ion levels is required for periodic contractions. We find spontaneous asynchronous calcium oscillations at stages before sarcomere assembly, indicating that this control system starts to be put in place prior to maturation of the contractile machinery. Using time-lapse imaging and inhibitor studies, we determine that the NCX1, a sodium-calcium exchanger, is essential for these calcium oscillations. Our work on the mouse suggest that the human heart starts to beat earlier than widely appreciated, perhaps as early as ~19 days after conception.

Tyser, R., Miranda, A., Chen, C-M., Davidson, S., M., Srinivas, S.* and Riley, P.* (2016) Calcium handling precedes cardiac differentiation to initiate the first heart beat. eLIFE 2016;5:e17113. DOI: 10.7554/eLife.17113. *Joint corresponding authors.