UC Davis

Reactive oxygen species (ROS) and electric currents modulate regeneration; however, the interplay between biochemical and biophysical signals during regeneration remains poorly understood. We investigate the interactions between redox and bioelectric activities during tail regeneration in Xenopus laevis tadpoles. We show that inhibition of NADPH oxidase-mediated production of ROS, or scavenging or blocking their diffusion into cells, impairs regeneration and consistently regulates the dynamics of membrane potential, transepithelial potential (TEP) and electric current densities (J_I) during regeneration. Depletion of ROS mimics the altered TEP and J_I observed in the non-regenerative refractory period. Short-term application of hydrogen peroxide (H₂O₂) rescues (from depleted ROS) and induces (from the refractory period) regeneration, TEP increase and J_I reversal. H₂O₂ is therefore necessary for and sufficient to induce regeneration and to regulate TEP and J_I Epistasis assays show that voltage-gated Na⁺ channels act downstream of H₂O₂ to modulate regeneration. Altogether, these results suggest a novel mechanism for regeneration via redox-bioelectric orchestration.