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 i...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.展开更多
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)+1 种基金Shanghai Leading Academic Discipline Project(B112 and T0302)NIH-HD3485
文摘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.
