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 Nav1.2 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。
Key Words δ-opioid Receptors - Na+ Channels - Na+ Currents - UFP-512 - Xenopus Oocytes - Excitability
关键词 δ-阿片受体 - 钠通道 - 钠电流 - UFP-512 - 爪蟾卵母细胞 - 兴奋性
CLC Number R2-03
Fund Items: 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) and Shanghai Leading Academic Discipline
Project (B112 and T0302), NIH-HD3485.
Author: KANG Xue-zhi, 27 years old, Research Assistant at SRCAM; main research interests:acupuncture and epilepsy
Corresponding Author: XIA Ying, 53 years old, Associate Professor at Yale University School of Medicine; main research interests: molecular neuroscience
and acupuncture mechanisms