Laboratory of Pharmacology, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Sapporo 060-0818, Japan.
Neurosci Lett. 2011 Jul 20;499(2):137-42. doi: 10.1016/j.neulet.2011.05.057. Epub 2011 May 30.
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+)) 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+) 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+) 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.
硫化氢 (H(2)S) 被认为是一种气体递质。尽管有几项报告表明 H(2)S 可刺激感觉神经元，但 H(2)S 的主要靶标仍存在争议。我们使用 Ca(2+) 成像和全细胞膜片钳技术研究了 H(2)S 对从大鼠背根神经节 (DRG) 分离培养的感觉神经元的影响。短暂（2 分钟）应用 H(2)S 的供体 NaHS（1mM）可引起部分 DRG 神经元细胞内 Ca(2+) 浓度 (Ca(2+)) 明显增加。这些神经元还分别对辣椒素和芥末油 (MO) 做出反应，MO 是瞬时受体电位香草醛 1 (TRPV1) 和锚蛋白 1 (TRPA1) 的激动剂。NaHS 诱发的 Ca(2+) 增加可被去除细胞外 Ca(2+) 和 TRPA1 拮抗剂抑制，但不能被 TRPV1 或电压依赖性 Ca(2+) 通道拮抗剂抑制。在 -80 mV 下，NaHS 诱发 MO 敏感神经元内向电流，该电流也可被 TRPA1 拮抗剂抑制。即使在较低浓度（≤1 μM）下，10 分钟的 NaHS 应用也以时间和浓度依赖的方式增加 Ca(2+)。这些结果表明 H(2)S 通过激活 TRPA1 刺激感觉神经元。内源性 H(2)S 可能通过 TRPA1 参与生理过程。
