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

Hydrogen sulfide (H(2)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 H(2)S and NO generates polysulfides (H(2)S(n)), which activate transient receptor potential ankyrin 1 (TRPA1) channels. High performance liquid chromatography with tandem mass spectrometry analysis, along with the imaging of intracellular Ca(2+) and H(2)S(n), showed that H(2)S(n) 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 H(2)S and NO interaction, are not affected by cyanolysis or reducing substances. This study demonstrates that H(2)S(n) are products of synergy between H(2)S and NO and provides a new insight into the signaling mechanisms.