Injury-induced electrochemical coupling triggers regenerative cell proliferation

Organ injury triggers non-neuronal electric currents essential for regeneration. Yet, the mechanisms by which electrical signals are generated, sensed and transmitted upon damage to promote organ growth remain unclear. Here, we uncover that organ regeneration relies on dynamic electrochemical coupling between tissue-wide depolarization and intracellular proliferative signalling. By sub-second live imaging of injured zebrafish larval fins, we identify events across timescales: a millisecond tissue depolarization gradient, followed by seconds-persistent intracellular Calcium responses. Subsequently within one hour, Voltage Sensing Phosphatase activity translates depolarisation into proliferation. Connecting these timescales with an electro-diffusive model showed that ionic fluxes and electric potential become coupled in the fins interstitial space, enabling organ-wide signal spreading. Our work reveals the coupling between fast electrical signals and slower intracellular signalling, ensuring organ regeneration.