ShanghaiTech University Knowledge Management System
| Differential roles of Na(V)1.2 and Na(V)1.6 in regulating neuronal excitability at febrile temperature and distinct contributions to febrile seizures | |
| 2018-01-15 | |
| Source Publication | SCIENTIFIC REPORTS
 |
| ISSN | 2045-2322 |
| Volume | 8 |
| Status | 已发表 |
| DOI | 10.1038/s41598-017-17344-8 |
| Abstract | Dysregulation of voltage-gated sodium channels (VGSCs) is associated with multiple clinical disorders, including febrile seizures (FS). The contribution of different sodium channel subtypes to environmentally triggered seizures is not well understood. Here we demonstrate that somatic and axonal sodium channels primarily mediated through Na(V)1.2 and Na(V)1.6 subtypes, respectively, behave differentially at FT, and might play distinct roles in FS generation. In contrast to sodium channels on the main axonal trunk, somatic ones are more resistant to inactivation and display significantly augmented currents, faster gating rates and kinetics of recovery from inactivation at FT, features that promote neuronal excitabilities. Pharmacological inhibition of N(a)V1.2 by Phrixotoxin-3 (PTx3) suppressed FT-induced neuronal hyperexcitability in brain slice, while up-regulation of Na(V)1.2 as in Na(V)1.6 knockout mice showed an opposite effect. Consistently, Na(V)1.6 knockout mice were more susceptible to FS, exhibiting much lower temperature threshold and shorter onset latency than wildtype mice. Neuron modeling further suggests that Na(V)1.2 is the major subtype mediating FT-induced neuronal hyperexcitability, and predicts potential outcomes of alterations in sodium channel subtype composition. Together, these data reveal a role of native Na(V)1.2 on neuronal excitability at FT and its important contribution to FS pathogenesis. |
| Indexed By | SCI ; SCIE |
| Language | 英语 |
| Funding Project | Postdoctor Research Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences[2012KIP507] |
| WOS Research Area | Science & Technology - Other Topics |
| WOS Subject | Multidisciplinary Sciences |
| WOS ID | WOS:000422637200012 |
| Publisher | NATURE PUBLISHING GROUP |
| WOS Keyword | SEVERE MYOCLONIC EPILEPSY ; GAIN-OF-FUNCTION ; SODIUM-CHANNEL SCN8A ; INFANTILE SEIZURES ; MOUSE MODEL ; SCN2A MUTATION ; GENE SCN2A ; MENTAL-RETARDATION ; SENSORY NEURONS ; NA+ CHANNELS |
| Original Document Type | Article |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/16231 |
| Collection | iHuman研究所_公共科研平台_超分辨生物成像平台 |
| Corresponding Author | Yang, Mingpo; Shu, Yousheng |
| Affiliation | 1.Beijing Normal Univ, Sch Brain & Cognit Sci, Collaborat Innovat Ctr Brain Sci, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, State Key Lab Neurosci, Shanghai, Peoples R China 3.ShanghaiTech Univ, iHuman Inst, Shanghai, Peoples R China 4.Capital Med Univ, Coll Pharmaceut Sci, Brain Inst, Beijing, Peoples R China |
| Recommended Citation GB/T 7714 | Ye, Mingyu,Yang, Jun,Tian, Cuiping,et al. Differential roles of Na(V)1.2 and Na(V)1.6 in regulating neuronal excitability at febrile temperature and distinct contributions to febrile seizures[J]. SCIENTIFIC REPORTS,2018,8. |
| APA | Ye, Mingyu.,Yang, Jun.,Tian, Cuiping.,Zhu, Qiyu.,Yin, Luping.,...&Shu, Yousheng.(2018).Differential roles of Na(V)1.2 and Na(V)1.6 in regulating neuronal excitability at febrile temperature and distinct contributions to febrile seizures.SCIENTIFIC REPORTS,8. |
| MLA | Ye, Mingyu,et al."Differential roles of Na(V)1.2 and Na(V)1.6 in regulating neuronal excitability at febrile temperature and distinct contributions to febrile seizures".SCIENTIFIC REPORTS 8(2018). |
| Files in This Item: | Download All | |||||
| File Name/Size | DocType | Version | Access | License | ||
Edit Comment
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.