Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Department of Systems Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Nature. 2023 Oct;622(7981):149-155. doi: 10.1038/s41586-023-06561-z. Epub 2023 Sep 27.
A regular heartbeat is essential to vertebrate life. In the mature heart, this function is driven by an anatomically localized pacemaker. By contrast, pacemaking capability is broadly distributed in the early embryonic heart, raising the question of how tissue-scale activity is first established and then maintained during embryonic development. The initial transition of the heart from silent to beating has never been characterized at the timescale of individual electrical events, and the structure in space and time of the early heartbeats remains poorly understood. Using all-optical electrophysiology, we captured the very first heartbeat of a zebrafish and analysed the development of cardiac excitability and conduction around this singular event. The first few beats appeared suddenly, had irregular interbeat intervals, propagated coherently across the primordial heart and emanated from loci that varied between animals and over time. The bioelectrical dynamics were well described by a noisy saddle-node on invariant circle bifurcation with action potential upstroke driven by Ca1.2. Our work shows how gradual and largely asynchronous development of single-cell bioelectrical properties produces a stereotyped and robust tissue-scale transition from quiescence to coordinated beating.
有规律的心跳对脊椎动物的生命至关重要。在成熟的心脏中，这一功能由解剖上定位的起搏器驱动。相比之下，起搏能力在早期胚胎心脏中广泛分布，这就提出了一个问题，即组织尺度的活动是如何首先建立的，然后在胚胎发育过程中维持。心脏从静止到跳动的最初转变从未在单个电事件的时间尺度上进行过描述，早期心跳的时空结构仍然知之甚少。我们使用全光学电生理学技术，捕捉到了斑马鱼的第一个心跳，并分析了围绕这个单一事件的心脏兴奋性和传导的发展。最初的几次跳动突然出现，心跳间隔不规则，在原始心脏中一致传播，并从不同动物和不同时间的位置发出。第一个生物电动力学很好地用一个噪声鞍结不变环分岔来描述，动作电位的上升由 Ca1.2 驱动。我们的工作表明，单细胞生物电特性的逐渐和大体上异步发展如何产生从静止到协调跳动的组织尺度的刻板和稳健的转变。
