Polysulfides are possible H 2 S‐derived signaling molecules in rat brain

Accumulating evidence shows that hydrogen sulfide (H 2 S) has a variety of physiological functions. H 2 S is produced from cysteine by 3 sulfurtransferases. H 2 S, in turn, generates polysulfides, the functions of which are not well understood. H 2 S induces Ca 2+ influx in astrocytes, a type of glia. However, the receptor that mediates the response has not been identified. Here, we have shown that polysulfides induce Ca 2+ influx by activating transient receptor potential (TRP)A1 channels in rat astrocytes (EC 50 91 nM, Hill coefficient value 1.77±0.26) and that the maximum response was induced at 0.5 μM, which is 1/320 of the concentration of H 2 S required to achieve a response of similar magnitude (160 μM, EC 50 116 μM). TRPA1‐selective agonists, allyl isothiocyanate and cinnamaldehyde, induced Ca 2+ influx, and responses to polysulfides were suppressed by TRPA1‐selective inhibitors, HC‐030031 and AP‐18, as well as by siRNAs selective to TRPA1. The present study suggests that polysulfides are possible H 2 S‐derived signaling molecules that stimulate TRP channels in the brain.—Kimura, Y., Mikami, Y., Osumi, K., Tsugane, M., Oka, J., Kimura, H. Polysulfides are possible H 2 S‐derived signaling molecules in rat brain. FASEB J. 27, 2451–2457 (2013). www.fasebj.org