Polysulfides (H 2 S n ) produced from the interaction of hydrogen sulfide (H 2 S) and nitric oxide (NO) activate TRPA1 channels.

Hydrogen sulfide (H2 S) exerts synergistic effects with another gaseous signaling molecule nitric oxide (NO) on ion channels and vasculature. However, the mechanism of the synergy is not well understood. Here, we show that the interaction between H2 S and NO generates polysulfides (H2 Sn ), which activate transient receptor potential ankyrin 1 (TRPA1) channels. High performance liquid chromatography with tandem mass spectrometry analysis, along with the imaging of intracellular Ca2+ and H2 Sn , showed that H2 Sn and their effects were abolished by cyanolysis and by reducing substances such as dithiothreitol (DTT), cysteine, and glutathione (GSH). However, the effects of nitroxyl or nitrosopersulfide, other potential products of H2 S and NO interaction, are not affected by cyanolysis or reducing substances. This study demonstrates that H2 Sn are products of synergy between H2 S and NO and provides a new insight into the signaling mechanisms.