Continuous release of O₂⁻/ONOO⁻ in plasma-exposed HEPES-buffered saline promotes TRP channel-mediated uptake of a large cation

Although the externally controllable extracellular supply of the short-lived reactive oxygen and nitrogen species, such as O₂^•−, ^•NO, and ONOO⁻, could potentially manipulate cellular functions, their simple administration to cells is likely to be ineffective due to their rapid deactivation. In this study, we found a method of a continuous supply of O₂^•−/ONOO⁻ over a few minutes, which is triggered by irradiation of a nonequilibrium atmospheric pressure plasma to commonly used organic buffers (e.g., 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, HEPES). In addition, a continuous low-dose O₂^•−/ONOO⁻ supply was shown to induce a physiologically relevant Ca²⁺ response and subsequently the uptake of a large cation mediated by transient receptor potential channel family member(s). Our results provide a novel approach to the continuous O₂^•−/ONOO⁻ supply, requiring controllable and mass-volume treatments.