Effects of (-) epigallocatechin-3-gallate on Na+ currents in rat dorsal root ganglion neurons
Effects of (-) epigallocatechin-3-gallate on Na+ currents in rat dorsal root ganglion neurons
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DOI：
10.1016/j.ejphar.2008.12.015
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发表时间：
2009-02-14
影响因子：
5
通讯作者：
Song, Jin-Ho
中科院分区：
文献类型：
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作者：
Kim, Tae Hoon;Lim, Jae-Min;Song, Jin-Ho
天然产物(-)表没食子儿茶素没食子酸酯(EGCG)是绿茶中发现的主要多酚成分。背根神经节神经元是主要的感觉神经元，表达河豚毒素敏感和河豚毒素抵抗的钠电流，这两种电流都积极参与伤害性信号的产生和传播。采用全细胞膜片钳技术，观察EGCG对大鼠背根神经节细胞河豚毒素敏感和河豚毒素抗性钠电流的影响。EGCG对这两种钠电流均有抑制作用，且呈浓度依赖关系。对河豚毒素敏感和抗河豚毒素的Na+电流，其表观解离常数K-d分别为0.74和0.80微米。(-)表没食子儿茶素(EGC)对Na+电流的抑制作用远低于EGCG，提示EGCG的没食子酸酯部分是调节Na+电流的重要功能基团。EGCG对上述两种Na+电流的激活电压或稳态失活电压几乎没有影响。EGCG只是减少了钠离子通道的激活。因此，EGCG似乎可以与静息的Na+通道结合来抑制它们。EGCG使河豚毒素敏感的Na+电流从失活状态缓慢恢复。EGCG抑制感觉性钠电流的特性可用于开发止痛药。(C)2008爱思唯尔B.V.保留所有权利。
The natural product(-) epigallocatechin-3-gallate (EGCG) is the major polyphenolic constituent found in green tea. Dorsal root ganglion neurons are primary sensory neurons, and express tetrodotoxin-sensitive and tetrodotoxin-resistant Na+ currents, which are both actively involved in the generation and propagation of nociceptive signals. Effects of EGCG on tetrodotoxin-sensitive and tetrodotoxin-resistant Na+ currents in rat dorsal root ganglion neurons were investigated using the whole-cell variation of the patch-clamp techniques. EGCG inhibited both types of Na+ currents potently and in a concentration-dependent manner. The apparent dissociation constant, K-d, was estimated to be 0.74 and 0.80 mu M for tetroclotoxin-sensitive and tetrodotoxin-resistant Na+ currents, respectively. (-) Epigallocatechin (EGC) was far less potent to inhibit Na+ currents than EGCG, suggesting that gallate moiety of EGCG is an important functional group to modulate Na+ currents. EGCG had little or no effect on the activation or steady-state inactivation voltage of either type of Na+ current. EGCG simply reduced the availability of Na+ channels for activation. Thus, EGCG appears to bind to resting Na+ channels to inhibit them. EGCG slowed the recovery of tetrodotoxin-sensitive Na+ current from inactivation. The property of EGCG to inhibit sensory Na+ currents can be utilized to develop an analgesic agent. (C) 2008 Elsevier B.V. All rights reserved.