Injury-induced electrochemical coupling triggers organ growth

Organ injury triggers nonneuronal electric currents essential for regeneration. However, the mechanisms by which electrical signals are generated, sensed, and transmitted upon damage to promote organ growth remain unclear. Here, we uncover that organ repair relies on dynamic electrochemical coupling between membrane potential depolarization and intracellular signaling, essential to activate cell proliferation. By subsecond live imaging of locally injured zebrafish larval fins, we identify events across time and space: a millisecond, long-range, membrane depolarization gradient, followed by second-persistent intracellular calcium responses. In the subsequent hour, voltage sensing phosphatase senses the injury-driven membrane potential change and autonomously translates the electric signal intracellularly, promoting tissue-wide cell proliferation. Connecting these dynamics with an electrodiffusive model showed that ionic fluxes and electric potential become coupled in the fin's interstitial space, enabling organ-wide signal spreading. Our work reveals the coupling between fast electrical signals and slower intracellular signaling, ensuring complete organ recovery.