UC Davis

For more than a century, the origin of the heartbeat has remained stubbornly elusive. The classical view was deterministic: a dominant cluster of the fastest cells entrains its neighbors, and the sinoatrial node delivers a clean, periodic impulse through a coupled system of membrane and Ca2+ clocks.1 The paradigm has endured, in part, because of experimental limits of resolution. With conventional optical mapping, pacemaking at the node emerges and progresses smoothly and uniformly from an initiation site. At higher spatial and temporal resolution, cell‑to‑cell variability emerges, revealing the sinoatrial node as a loosely coupled, brain‑like network of diversely firing and non‑firing cells in which subthreshold Ca2+ and voltage fluctuations are dispersed throughout the node.2,3