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.
KANG Xue-zhi GU Quan-bao DING Guang-hong CHAO Dong-man WANG Ying-wei G Balboni LH Lazarus XIA Ying
Shanghai Research Center of Acupuncture and Meridian,Shanghai 201203,China Yale University School of Medicine,New Haven,USA Shanghai Jiaotong University College of Medicine,Shanghai 200030,China University of Cagliari,Cagliari,Italy National Institute of Environmental Health Sciences,Research Triangle Park,USA Shanghai Research Center of Acupuncture and Meridian,Shanghai 201203,China;Yale University School of