Exogenous application of electricity via sub-threshold direct current stimulation (DCS) can induce a cellular or tissue-level response. Stem cells are particularly affected by electric stimulation, but the molecular basis of the response to DCS is largely unknown. In this work (Davidian et al., 2022), Néstor Oviedo and colleagues assess the real-time response to DCS in immobilised irradiated planaria – a technique they term pDCS. Planaria have a high rate of cellular turnover and remarkable regenerative capacity owing to adult stem cells called neoblasts. After exposing planaria to ionising radiation to eliminate their neoblasts, the authors grafted tissue containing neoblasts onto the irradiated worms and applied DCS. They found that pDCS restores stem cell features in irradiated planaria, marked by the expression of piwi-1 and other neoblast sub-class-related genes that had been eliminated by radiation. This was accompanied by the expression of genes associated with cell cycle regulation, transcriptional activation and DNA-damage repair response in tissues exposed to lethal doses of ionising radiation. Furthermore, the authors found that DCS-mediated responses involved rapid increases in cytosolic [Ca2+] via activation of L-type Cav channels and intracellular Ca2+ stores, resulting in transcription of immediate early genes and stem cell marker expression in postmitotic cells. These findings describe how electric stimulation results in a molecular response, with promising results for the role of DCS in reversing high-dose radiation damage in adult tissues.
