title: Synergetic action of domain II and IV underlies persistent current generation in Nav1.3 as revealed by a tarantula toxin.
abstract: The persistent current (INaP) through voltage-gated sodium channels enhances neuronal excitability by causing prolonged depolarization of membranes. Nav1.3 intrinsically generates a small INaP, although the mechanism underlying its generation remains unclear. In this study, the involvement of the four domains of Nav1.3 in INaP generation was investigated using the tarantula toxin α-hexatoxin-MrVII (RTX-VII). RTX-VII activated Nav1.3 and induced a large INaP. A pre-activated state binding model was proposed to explain the kinetics of toxin-channel interaction. Of the four domains of Nav1.3, both domain II and IV might play important roles in the toxin-induced INaP. Domain IV constructed the binding site for RTX-VII, while domain II might not participate in interacting with RTX-VII but could determine the efficacy of RTX-VII. Our results based on the use of RTX-VII as a probe suggest that domain II and IV cooperatively contribute to the generation of INaP in Nav1.3.
authors.affiliation: College of Life Science, Hunan Normal University, Changsha, Hunan. 410081, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Tang
authors.affiliation: College of Life Science, Hunan Normal University, Changsha, Hunan. 410081, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhou
authors.affiliation: College of Life Science, Hunan Normal University, Changsha, Hunan. 410081, China.
authors.forename: Yunxiao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Xiangya Hospital of Central South University, Changsha, Hunan. 410008, China.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: College of Life Science, Hunan Normal University, Changsha, Hunan. 410081, China.
authors.forename: Zhaotun
authors.initials: Z
authors.lastname: Hu
authors.affiliation: College of Life Science, Hunan Normal University, Changsha, Hunan. 410081, China.
authors.forename: Changxin
authors.initials: C
authors.lastname: Zhang
authors.affiliation: College of Life Science, Hunan Normal University, Changsha, Hunan. 410081, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: College of Life Science, Hunan Normal University, Changsha, Hunan. 410081, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.affiliation: College of Life Science, Hunan Normal University, Changsha, Hunan. 410081, China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Liu
authors.affiliation: College of Life Science, Hunan Normal University, Changsha, Hunan. 410081, China.
authors.forename: Songping
authors.initials: S
authors.lastname: Liang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008564:Membrane Potentials; D051379:Mice; D008969:Molecular Sequence Data; D062552:NAV1.3 Voltage-Gated Sodium Channel / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000737:chemistry / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D016415:Sequence Alignment; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013112:Spiders / Q000378:metabolism; D014118:Toxins, Biological / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D062552:NAV1.3 Voltage-Gated Sodium Channel; D062554:NAV1.5 Voltage-Gated Sodium Channel; C424715:SCN3A protein, human; C568320:SCN5A protein, human; D015222:Sodium Channels; D014118:Toxins, Biological