δ-opioid Receptor Induced Inhibition of Sodium Channel Function  

作　　者：康学智 顾全保 丁光宏 晁东满 王英伟 G Balboni LH Lazarus 夏萤 

机构地区：[1]Shanghai Research Center of Acupuncture and Meridian,Shanghai 201203,China [2]Yale University School of Medicine,New Haven,USA [3]Shanghai Jiaotong University College of Medicine,Shanghai 200030,China [4]University of Cagliari,Cagliari,Italy [5]National Institute of Environmental Health Sciences,Research Triangle Park,USA [6]Shanghai Research Center of Acupuncture and Meridian,Shanghai 201203,China Yale University School of Medicine,New Haven,USA

出　　处：《Journal of Acupuncture and Tuina Science》2008年第5期276-278,共3页针灸推拿医学（英文版）

基　　金：the Science Foundation of Shanghai Municipal Commission of Science and Technology(05DZ19745,06DZ19732,064319053,07DZ19722,07DZ19733);the National Basic Research Program of China(973 Program,2005CB523306);Shanghai Leading Academic Discipline Project(B112 and T0302);NIH-HD3485

摘　　要：Objective： To study the precise role of DOR in the regulation of sodium channels at present. Methods： With Xenopus oocytes co-expressing sodium channel subtype 2 （Nav1.2） and DOR. Results： 1） Nav1.2 expression induced tetrodotoxin-sensitive inward currents; 2） DOR expression reduced the inward currents; 3） activation of DOR reduced the amplitude of the current and rightly shifted the activation curve of the current in the oocytes with both Nav1.2 and DOR, but not in ones with Nav1.2 alone; 4） the DOR agonist-induced inhibition of Nay 1.2 currents was in a dose-dependent manner and saturable; 5） the DOR agonist had no effect on naive oocytes. Conclusion： These data represent the first demonstration that activation of DOR inhibits Na^＋ channel function by decreasing the amplitude of sodium currents and increasing its threshold of activation. This novel finding has far-reaching impacts on novel solutions of certain neurological disorders such as hypoxic/ischemic injury, epilepsy and pain. Also, our data may improve the understanding of the mechanisms underlying acupuncture since acupuncture is known to activate the brain opioid system.目的:研究δ-阿片受体表达和激活对钠通道1.2亚型的电流特性的影响。方法:用双电极电压钳技术,在δ-阿片受体和钠通道亚型1.2共表达的非洲爪蟾第 V 期卵母细胞上,观察δ-阿片受体表达和/或激活后,钠通道1.2亚型电流特性的变化。结果:1)钠通道1.2亚型的表达产生河豚毒素(tetrodotoxin,TTX)敏感的内向电流;2)δ-阿片受体的表达减少钠通道激活电流的幅度;3)δ-阿片受体和钠通道1.2亚型共表达的卵母细胞中,δ-阿片受体激动剂可以抑制钠通道激活电流的幅度和电导,而只有钠通道1.2亚型表达的卵母细胞则无此现象;4)δ-阿片受体激动剂抑制钠电流的作用具有剂量依赖关系,并能达到饱和状态;5)δ-阿片受体激动剂对未表达外源性蛋白的卵母细胞无影响。结论:本结果首次以直接证据证明了δ-阿片受体可以抑制钠通道的兴奋性和降低钠电流的幅度。这一发现对缺血/缺氧性神经元损伤、癫痫、疼痛等神经机能障碍的解决具有深远意义,并有助于深入揭示针刺治疗脑疾病的内在机制。

关 键 词：δ-opioid Receptors Na^＋ Channels Na^＋ Currents UFP-512 Xenopus Oocytes EXCITABILITY 

分 类 号：R2-03[医药卫生—中医学]