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

doi:10.1038/s41598-017-17344-8

	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
	Ye, Mingyu 2; Yang, Jun 1; Tian, Cuiping3 ; Zhu, Qiyu 4; Yin, Luping 1; Jiang, Shan 2; Yang, Mingpo 2; Shu, Yousheng 1
	2018-01-15
发表期刊	SCIENTIFIC REPORTS
ISSN	2045-2322
卷号	8
发表状态	已发表
DOI	10.1038/s41598-017-17344-8
摘要	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.
收录类别	SCI ; SCIE
语种	英语
资助项目	Postdoctor Research Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences[2012KIP507]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000422637200012
出版者	NATURE PUBLISHING GROUP
WOS关键词	SEVERE MYOCLONIC EPILEPSY ; GAIN-OF-FUNCTION ; SODIUM-CHANNEL SCN8A ; INFANTILE SEIZURES ; MOUSE MODEL ; SCN2A MUTATION ; GENE SCN2A ; MENTAL-RETARDATION ; SENSORY NEURONS ; NA+ CHANNELS
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/16231
专题	iHuman研究所_公共科研平台_超分辨生物成像平台
通讯作者	Yang, Mingpo; Shu, Yousheng
作者单位	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
推荐引用方式 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).