title: Time- and concentration-dependent activation of TRPA1 by hydrogen sulfide in rat DRG neurons.
abstract: Hydrogen sulfide (H(2)S) is considered as a gasotransmitter. Although several reports have shown that H(2)S stimulates sensory neurons, the primary targets of H(2)S remain controversial. We investigated the effects of H(2)S on cultured sensory neurons isolated from rat dorsal root ganglion (DRG) using Ca(2+) imaging and whole-cell voltage-clamp techniques. Brief (2 min) application of NaHS (1mM), a donor of H(2)S, evoked marked increases in intracellular Ca(2+) concentration ([Ca(2+)](i)) in a subset of DRG neurons. These neurons also responded to both capsaicin and mustard oil (MO), transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) agonists, respectively. The NaHS-evoked [Ca(2+)](i) increases were inhibited by a removal of external Ca(2+) and antagonists for TRPA1, but not for TRPV1 or voltage-dependent Ca(2+) channels. At -80 mV, NaHS evoked inward currents in MO-sensitive neurons, which were also inhibited by a TRPA1 antagonist. Even at lower concentration (≤1 μM), the 10-min application of NaHS increased [Ca(2+)](i) in a time- and concentration-dependent manner. These results suggest that H(2)S stimulates sensory neurons via activation of TRPA1. Endogenous H(2)S may be involved in physiological processes through TRPA1.
authors.affiliation: Laboratory of Pharmacology, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Sapporo 060-0818, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Miyamoto
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Otsuguro
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ito
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000819:agonists / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; D006862:Hydrogen Sulfide