EFFECT OF RESINIFERATOXIN ON GLUTAMATERGIC SPONTANEOUS EXCITATORY SYNAPTIC TRANSMISSION IN SUBSTANTIA GELATINOSA NEURONS OF THE ADULT RAT SPINAL CORD
EFFECT OF RESINIFERATOXIN ON GLUTAMATERGIC SPONTANEOUS EXCITATORY SYNAPTIC TRANSMISSION IN SUBSTANTIA GELATINOSA NEURONS OF THE ADULT RAT SPINAL CORD
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DOI：
10.1016/j.neuroscience.2009.09.033
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发表时间：
2009-12-29
期刊：
影响因子：
3.3
通讯作者：
Kumamoto, E.
中科院分区：
文献类型：
--
作者：
Jiang, C. -Y.;Fujita, T.;Kumamoto, E.
瞬时受体电位（TRP）香草素1型（TRPV 1）激动剂辣椒素可增强CNS神经元中的多巴胺能自发兴奋性突触传递。树脂毒素（RTX）对TRPV 1的亲和力比辣椒素高得多，但其调节兴奋性传递的能力尚不清楚。采用全细胞膜片钳技术研究了RTX对成年大鼠脊髓片胶状质神经元兴奋性传递的影响。RTX剂量依赖性地增加自发兴奋性突触后电流（sEPSC）的频率，但不增加振幅，与其应用时间无关。在大约一半的测试神经元中，这种效应伴随着对谷氨酸受体拮抗剂敏感的-70 mV的内向电流。重复应用RTX不影响兴奋性传递。RTX比辣椒素更有效，但表现出相似的功效。RTX活性可以被辣椒平或SB-366791（TRPV 1拮抗剂）阻断，但不能被河豚毒素（Na+通道阻断剂）阻断，并且可以被辣椒素预处理抑制，但不能被TRPA 1激动剂异硫氰酸烯丙酯抑制。RTX以与辣椒素类似的功效增强L-谷氨酸从神经末梢的自发释放，并通过激活SG中的TRPV 1产生膜去极化，具有快速脱敏和从脱敏中缓慢恢复。这些结果表明RTX可以通过调节SG神经元中的兴奋性传递来调节伤害性传递的机制。(C)2009年IBRO。由爱思唯尔有限公司出版。保留所有权利。
The transient receptor potential (TRP) vanilloid type 1 (TRPV1) agonist, capsaicin, enhances glutamatergic spontaneous excitatory synaptic transmission in CNS neurons. Resiniferatoxin (RTX) has a much higher affinity for TRPV1 than capsaicin, but its ability to modulate excitatory transmission is unclear. We examined the effect of RTX on excitatory transmission using the whole-cell patch-clamp technique in substantia gelatinosa (SG) neurons of adult rat spinal cord slices. Bath-applied RTX dose-dependently increased the frequency, but not the amplitude, of spontaneous excitatory postsynaptic current (sEPSC), independent of its application time. In about a half of the neurons tested, this effect was accompanied by an inward current at -70 mV that was sensitive to glutamate-receptor antagonists. Repeated application of RTX did not affect excitatory transmission. RTX was more potent than capsaicin but showed similar efficacy. RTX activity could be blocked by capsazepine or SB-366791, a TRPV1 antagonist, but not tetrodotoxin, a Na+-channel blocker, and could be inhibited by pretreatment with capsaicin but not the TRPA1 agonist, allyl isothiocyanate. RTX enhances the spontaneous release Of L-glutamate from nerve terminals with similar efficacy as capsaicin and produces a membrane depolarization by activating TRPV1 in the SG, with fast desensitization and slow recovery from desensitization. These results indicate a mechanism by which RTX can modulate excitatory transmission in SG neurons to regulate nociceptive transmission. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.