Distribution and Functional Characteristics of Voltage-Gated Sodium Channels in Immature Cochlear Hair Cells

作     者：You Zhou Chenchen Xia Manli Yi Xueling Wang Hao Wu Yonghua Ji You Zhou;Chenchen Xia;Manli Yin;Xueling Wang;Hao Wu;Yonghua Ji

作者机构：Department of Otolaryngology-Head and Neck SurgeryNinth People’s HospitalShanghai Jiaotong University School of MedicineShanghai 200125China Ear InstituteShanghai Jiaotong University School of MedicineShanghai 200125China Shanghai Key Laboratory of Translational Medicine on Ear and Nose DiseasesShanghai 200125China Laboratory of Neuropharmacology and NeurotoxicologyShanghai UniversityShanghai 200444China Translational Institute for Cancer PainXinhua Hospital Chongming BranchShanghai 202150China 

出 版 物：《Neuroscience Bulletin》 (神经科学通报（英文版）)

年 卷 期：2020年第36卷第1期

页      面：49-65页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100213[医学-耳鼻咽喉科学] 10[医学] 

基　　金：We thank Prof.Lin Chen(University of Science and Technology of China)and Dr.Juanmei Yang(Eye and ENT Hospital of Fudan University)for valuable help with cochlear microscopic anatomy.This work was supported by the National Natural Science Foundation of China(31571032,31771191.81730028) the National Basic Research Development Program of China(SQ2017YFSF080012) the Postdoctoral Science Foundation of China(2018M640407) 

主　　题：Cochlear hair cell Spontaneous action potential Voltage-gated sodium channel Post-transcriptional modification Gating property Introduction 

摘      要：Voltage-gated sodium channels(VGSCs)are transiently expressed in cochlear hair cells before hearing onset and play an indispensable role in shaping spontaneous *** this study,we showed that Na^+currents shaped the spontaneous action potentials in developing mouse inner hair cells(IHCs)by decreasing the time required for the membrane potential to reach the action-potential *** immature IHCs,we identified 9 known VGSC subtypes(***-l.9ot),among which Navl.7a was the most highly expressed subtype and the main contributor to Na+currents in developing hair *** recordings of two cochlea-specific Navi.7 variants(CbmNavl.7a and CbmNavl.7b)revealed a novel loss-of-function mutation(C934R)at the extracellular linker between segments 5 and 6 of domain *** addition,post-transcriptional modification events,such as alternative splicing and RNA editing,amended the gating properties and kinetic features of CbmNavl.7a(C934).These results provide molecular and functional characteristics of VGSCs in mammalian IHCs and their contributions to spontaneous physiological activity during cochlear maturation.