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 PublicationSCIENTIFIC REPORTS
ISSN2045-2322
Volume8
Status已发表
DOI10.1038/s41598-017-17344-8
AbstractDysregulation 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 BySCI ; SCIE
Language英语
Funding ProjectPostdoctor Research Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences[2012KIP507]
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000422637200012
PublisherNATURE PUBLISHING GROUP
WOS KeywordSEVERE MYOCLONIC EPILEPSY ; GAIN-OF-FUNCTION ; SODIUM-CHANNEL SCN8A ; INFANTILE SEIZURES ; MOUSE MODEL ; SCN2A MUTATION ; GENE SCN2A ; MENTAL-RETARDATION ; SENSORY NEURONS ; NA+ CHANNELS
Original Document TypeArticle
Citation statistics
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/16231
CollectioniHuman研究所_公共科研平台_超分辨生物成像平台
Corresponding AuthorYang, 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).
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