In vivo patch-clamp analysis of the antinociceptive actions of TRPA1 activation in the spinal dorsal horn.
In vivo patch-clamp analysis of the antinociceptive actions of TRPA1 activation in the spinal dorsal horn.
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DOI：
10.1186/s12990-015-0021-6
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发表时间：
2015-04-21
期刊：
影响因子：
3.3
通讯作者：
Nakatsuka T
中科院分区：
文献类型：
--
作者：
Yamanaka M;Taniguchi W;Nishio N;Hashizume H;Yamada H;Yoshida M;Nakatsuka T
瞬时受体电位（TRP）通道是在多种感觉结构中表达的非选择性阳离子通道，是热、机械、细胞和化学信号的重要分子介质。我们使用体内膜片钳记录研究了 TRP 超家族的一个关键成员 TRPA1 在脊髓背角的功能。 TRPA1 激动剂异硫氰酸烯丙酯 (AITC) 的应用显着增加了凝胶质 (SG) 神经元中抑制性突触后电流 (IPSC；保持电位 (VH) = 0 mV) 以及兴奋性突触后电流 (EPSC；VH = −70 mV) 的频率和幅度。 AITC 诱导的 EPSC 频率和振幅增加对 Na+ 通道阻断剂河豚毒素 (TTX) 具有抵抗力。在谷氨酸受体拮抗剂 CNQX 和 AP5 存在的情况下，AITC 不产生任何突触活性。 AITC 诱导的 IPSC 频率和振幅增加被 TTX 或谷氨酸受体拮抗剂消除。此外，TRPA1激活增强的IPSCs的持续时间明显长于脊髓背角中该通道激活增强的EPSCs的持续时间。 AITC 诱导脊髓中 SG 神经元的膜电位超极化，但在 TTX 存在的情况下使膜电位去极化。此外，我们在电压钳和电流钳模式下检查了正常大鼠脊髓背角 TRPA1 激活过程中机械刺激对皮肤的影响。在外周组织刺激测试中，AITC 显着抑制由皮肤捏捏或吹气刺激引起的 EPSC。在电流钳模式下，AITC 显着抑制由捏刺激引起的兴奋性突触后电位 (EPSP)。 TRPA1 似乎不仅定位于 SG 神经元的突触前末端，增强谷氨酸的释放，而且还定位于支配脊髓抑制性中间神经元的初级传入神经的末端，这些神经元与 SG 神经元有突触相互作用。这项研究进一步深入了解了脊髓背角 TRPA1 激活可能产生的抗伤害作用的机制。我们的研究结果表明，脊髓 TRPA1 通道的药理激活可能具有治疗疼痛的潜力。
Transient receptor potential (TRP) channels are nonselective cation channels expressed in a variety of sensory structures, and are important molecular mediators of thermal, mechanical, cellular and chemical signals. We investigated the function of one key member of the TRP superfamily, TRPA1, in the spinal dorsal horn using in vivo patch-clamp recordings. The application of allyl isothiocyanate (AITC), a TRPA1 agonist, significantly increased the frequency and amplitude of inhibitory postsynaptic currents (IPSCs; holding potential (VH) = 0 mV) as well as excitatory postsynaptic currents (EPSCs; VH = −70 mV) in substantia gelatinosa (SG) neurons. The AITC-induced increases in EPSC frequency and amplitude were resistant to the Na+ channel blocker tetrodotoxin (TTX). In the presence of the glutamate receptor antagonists CNQX and AP5, AITC did not generate any synaptic activity. The AITC-induced increases in IPSC frequency and amplitude were abolished by TTX or glutamate receptor antagonists. Moreover, the duration of IPSCs enhanced by TRPA1 activation were significantly longer than those of EPSCs enhanced by activation of this channel in the spinal dorsal horn. AITC induced hyperpolarization of the membrane potential of SG neurons in the spinal cord but depolarized the membrane potential in the presence of TTX. Furthermore, we examined the effects of mechanical stimuli to the skin during TRPA1 activation in the spinal dorsal horn in normal rats in both voltage-clamp and current-clamp modes. In the peripheral tissue stimuli test, AITC significantly suppressed EPSCs evoked by pinch or air puff stimulation of the skin. In current-clamp mode, AITC significantly suppressed excitatory postsynaptic potentials (EPSPs) evoked by pinch stimuli. TRPA1 appears to be localized not only at presynaptic terminals on SG neurons, enhancing glutamate release, but also in the terminals of primary afferents innervating spinal inhibitory interneurons, which have synaptic interactions with SG neurons. This study offers further insight into the mechanisms underlying the possible antinociceptive actions of TRPA1 activation in the spinal dorsal horn. Our findings suggest that pharmacological activation of spinal TRPA1 channels may have therapeutic potential for the treatment of pain.
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DOI：
10.1002/neu.20079
发表时间：
2004-10-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Tominaga, M;Caterina, MJ
通讯作者：
Caterina, MJ
影响因子：
16.2
作者：
Kwan, KY;Allchorne, AJ;Corey, DP
通讯作者：
Corey, DP
影响因子：
5.3
作者：
Kosugi, Masafumi;Nakatsuka, Terumasa;Kumamoto, Eiichi
通讯作者：
Kumamoto, Eiichi
影响因子：
5.3
作者：
Nagata, K;Duggan, A;García-Añoveros, J
通讯作者：
García-Añoveros, J
影响因子：
4.5
作者：
Miyazaki, Nobuyuki;Nakatsuka, Terumasa;Yoshida, Munehito
通讯作者：
Yoshida, Munehito