Pulsation waves along the Ciona heart tube reverse by bimodal rhythms expressed by a remote pair of pacemakers

The heart of ascidians, marine invertebrate chordates, exhibits a tubular structure, and heartbeats propagate from one end to the other. The direction of pulsation waves intermittently reverses in the heart of ascidians and their relatives; however, the underlying mechanisms remain unclear. We herein performed a series of experiments to characterize the pacemaker systems in isolated hearts and their fragments and applied a mathematical model to examine the conditions leading to heart reversals. The isolated heart of Ciona sufficiently performed heart reversals, and experimental bisections of isolated hearts revealed that independent pacemakers resided on each side and also that their beating frequencies periodically changed as they expressed bimodal rhythms. Only fragments including 5% or shorter terminal regions of the heart tube maintained autonomous pulsation rhythms, whereas other regions did not. Our mathematical model, based on FitzHugh-Nagumo equations applied to a one-dimensional alignment of cells, demonstrated that the difference between frequencies expressed by the two independent terminal pacemakers determined the direction of propagated waves. Changes in the statuses of the terminal pacemakers between the excitatory and oscillatory modes as well as in their endogenous oscillation frequencies were sufficient to lead to heart reversals. These results suggest that the directions of pulsation waves in the Ciona heart reverse according to the changing rhythms independently expressed by remotely coupled terminal pacemakers. Summary statementPulsation waves traveling along the heart tube of the ascidian Ciona intermittently reverse because of autonomous and periodical changes in beating frequencies at a pair of terminal pacemakers.