Time- and concentration-dependent activation of TRPA1 by hydrogen sulfide in rat DRG neurons

Time- and concentration-dependent activation of TRPA1 by hydrogen sulfide in rat DRG neurons
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DOI:
10.1016/j.neulet.2011.05.057
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发表时间:
2011-07-20
影响因子:
2.5
通讯作者:
Ito, Shigeo
Ito, Shigeo
中科院分区:
医学4区
文献类型:
--
作者:
Miyamoto, Ryo;Otsuguro, Ken-ichi;Ito, Shigeo

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硫化氢(H(2)S)被认为是一种气体递质。虽然有几份报告表明H(2)S刺激感觉神经元,但H(2)S的主要靶点仍然存在争议。采用Ca(2+)显像和全细胞电压钳技术研究了硫化氢(H(2)S)对大鼠背根神经节(DRG)感觉神经元的影响。短暂(2分钟)应用NaHS(1 mM),H(2)S的供体,在DRG神经元亚群中引起细胞内Ca(2+)浓度([Ca(2+)](i))的显著增加。这些神经元还分别对辣椒素和芥子油(MO)、瞬时受体电位香草素1(TRPV 1)和锚蛋白1(TRPA 1)激动剂产生反应。NaHS诱发的[Ca(2+)](i)增加可被去除外部Ca(2+)和TRPA 1拮抗剂抑制,但不抑制TRPV 1或电压依赖性Ca(2+)通道。在-80 mV时,NaHS在MO敏感神经元中诱发内向电流,该电流也被TRPA 1拮抗剂抑制。即使在较低浓度下(
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 (1 mM), 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 (