Early bioelectric activities mediate redox-modulated regeneration

Abstract

Reactive oxygen species (ROS) and electric currents modulate regeneration; however, the interplays between biochemical and biophysical signals during regeneration remain poorly understood. We investigate the interactions between redox and bioelectric activities during tail regeneration in Xenopus laevis tadpoles. We show that inhibition of NADPH oxidases-mediated production of ROS, or scavenging or blocking their diffusion into cells, impairs regeneration and consistently regulate the dynamics of membrane potential, transepithelial potential (TEP) and electric current densities (JI) during regeneration. Depletion of ROS mimics the altered TEP and JI observed in the non-regenerative refractory period. Short-term application of hydrogen peroxide (H2O2) rescues (from depleted ROS) and gains (from refractory period) regeneration, TEP increase and JI reversal. H2O2 is thereby necessary for and sufficient to induce regeneration and to regulate TEP and JI. 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.