How the heart begins to beat

The video is moving... even if it only concerns a zebrafish. We witness a key moment in the beginning of life: the animal’s very first heartbeat. This was observed by researchers from the department of chemistry and biology at the prestigious American University of Harvard, who managed to film and characterize the first heartbeats in embryos. A crucial stage for the development of the organism, which until then had never been observed, and of which we did not know how it took place.

In a mature heart, cells contract synchronously thanks to a zone acting as a “pacemaker”, sending periodic electrical impulses through the organ which synchronize its contractions. But the first cardiac cells did not have such a “pacemaker”. How do they start to beat in unison? Is it at first the most complete disorder, each one starting by beating at its own rhythm before coming into agreement with all the others? Several hypotheses had been put forward, but none could be confirmed.

In a study published in Nature, Harvard researchers show that these beats quickly become synchronous. They used zebrafish (a small laboratory fish measuring 4 to 5 cm), because “its transparency and the development of the embryo outside the mother make it practical to observe the organs,” explains Anabela Bensimon-Brito, researcher in homeostasis and cardiovascular at CBI-MBD, in Toulouse. Zebrafish fetuses were manipulated so that heart cells fluoresced green or red when they exchanged calcium. These exchanges occur when a heart cell contracts.

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First observation of the study: the heart cells suddenly go from no movement to the first regular beats, and all this synchronously (with the same rhythm). “It’s like someone flipped a switch,” Adam Cohen, a researcher at Harvard University, described in a press release. Anabela Bensimon-Brito confirms that “the first non-regular contractions are at the origin of a wave, which then synchronizes the cells to the same rhythm”.

Second lesson, a region of the heart begins to beat first, and sends electrical signals to the rest of the heart cells to trigger contractions. But this initiating region varies from one fish to another. So there is no specific initiating region, as the researchers might have thought.

18 zebrafish embryos observed under a microscope. Fluorescence shows calcium utilization in embryonic hearts. Some individuals have not started using calcium (no fluorescence) while others have already synchronized calcium use (fluorescence flashes) essential for regular heartbeats. (Credit: Bill Jia, Harvard University).

“The heart first learns to follow the rhythm without a clock, and individual cells first learn to cooperate without agreeing on their roles,” added Bille Jia, first author of the study, in the same press release. , researcher in biology and chemistry at Harvard. “It's very important that the heartbeat be regular, but it organizes itself very quickly early in life from what seems like a total mess. »

Could the mechanisms observed in this zebrafish, a vertebrate, be observed in humans? Would knowing them better help to understand heart rhythm disorders, in the hope of preventing and treating them? “The phases of cardiac development are similar between fish and mammals, but there are differences between these two types of hearts,” specifies Alain Lacampagne, researcher in cardiac physiology and CNRS 2023 silver medalist. state of planning the health use of this fundamental research work. We are left to dream while contemplating a heart that begins to beat...