title: A novel μ-conotoxin from worm-hunting Conus tessulatus that selectively inhibit rat TTX-resistant sodium currents.
abstract: μ-conotoxins are a group of marine Conus peptides that inhibit sodium currents, so μ-conotoxins are valuable in sodium channel research and new analgesic drug discovery. Here, a novel μ-conotoxin TsIIIA was identified from a worm-hunting Conus tessulatus. TsIIIA was chemical synthesized according to its amino acid sequence GCCRWPCPSRCGMARCCSS and identified by mass spectrum. Patch clamp on rat dorsal root ganglion cells showed that 10 μM TsIIIA specifically inhibit TTX-resistant sodium currents but has no effect on TTX-sensitive sodium currents. TsIIIA inhibits TTX-resistant sodium currents by a dose-dependent mode with an IC50of 2.61 μM. Further study showed 10 μM TsIIIA has no obvious effect on the current-voltage relationships, conductance-voltage relationships and voltage-dependence of steady-state inactivation of TTX-resistant sodium channels. Mice hotplate analgesic assay indicated that TsIIIA obviously increase the pain threshold at 0.5-4 h. In addition, TsIIIA has better analgesic effects than Ziconotide, indicating that TsIIIA was a valuable lead compound for development of new analgesic drug.
authors.affiliation: Key Laboratory of Nanobiological Technology of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
authors.forename: Manyi
authors.initials: M
authors.lastname: Yang
authors.affiliation: Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Min
authors.affiliation: Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
authors.forename: Meiying
authors.initials: M
authors.lastname: Shao
authors.affiliation: Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
authors.forename: Yongheng
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
authors.forename: Zhuchu
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China. Electronic address: 280199518@qq.com.
authors.forename: Maojun
authors.initials: M
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D003001:Cloning, Molecular; D020916:Conotoxins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010146:Pain / Q000188:drug therapy; D018408:Patch-Clamp Techniques; D051381:Rats; D017422:Sequence Analysis, DNA; D020539:Sequence Analysis, Protein; D026941:Sodium Channel Blockers / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D020916:Conotoxins; D026941:Sodium Channel Blockers; C000623319:TSIIIA conotoxin, Conus tessulatus; D013779:Tetrodotoxin
keywords: Conopeptide; Conotoxin; Pain; Voltage-gated sodium channels