Activating Na＿v1.9 Recovers Pain Responses in Na＿v1.7-related CIP as Revealed by a Spider Toxin
作者单位：The National and Local Joint Engineering Laboratory of Animal Peptide Drug DevelopmentCollege of Life SciencesHunan Normal University Key Laboratory of Molecular Biophysics of the Ministry of EducationCollege of Life Science and TechnologyHuazhong University of Science and Technology(HUST) Department of AnesthesiologyTongji Hospital of HUST
会议名称：《第十四届生物毒素毒理学术大会暨第一届生物毒素——从生存适应到转化医学专题学术会议》
会议日期：2019年
学科分类：1006[医学-中西医结合] 1002[医学-临床医学] 100602[医学-中西医结合临床] 10[医学]
摘 要：In peripheral nociceptor,Na1.7,Na1.8 and Na1.9 are critical for pain ***,loss-of-function of Na1.7 leads to congenital insensitivity to pain(CIP) in humans,which causes individuals to loss the warning system and thus suffer from recurrent tissue damage and serious *** far,the therapeutic agents for treating the Nav1.7-related CEP are still in its *** we identified and characterized a spider peptide toxin called HpTx1 that reverses alganesthesia in Na1.7-KO mice by enhancing the excitability of DRG *** elucidate this process,we conformed that HpTxl inhibits Na 1.7(IC=0.51±0.12 μM),but it activates Nav 1.9(EC=0.47±0.08 μM) and has no effects on ***,HpTx1 reduces dorsal root ganglion(DRG) neurons excitability and produces analgesia in Na1.9-KO mice,and losses its effectiveness in Na1.8-KO mice These data indicated the pain-inducing effect by HpTxl should be mediated by Na1.9 ***,we found that HpTxl interacts with DIV s3 b-s4 of Na1.9 and DII s3 b-s4 of Na1.7,respectively,which explains its opposite effects on the two *** together,our findings suggest that Na1.9 agonists such as HpTx1 may be potential for the development of drugs to treat Na1.7-related CIP,and propose that Na1.7,Na1.8 and Na1.9 are interrelated in pain signaling.