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

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Abstract

Voltage-gated sodium channels (VGSCs) are transiently expressed in cochlear hair cells before hearing onset and play an indispensable role in shaping spontaneous activity. In 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 threshold. In immature IHCs, we identified 9 known VGSC subtypes (Nav1.1α–1.9α), among which Nav1.7α was the most highly expressed subtype and the main contributor to Na+ currents in developing hair cells. Electrophysiological recordings of two cochlea-specific Nav1.7 variants (CbmNav1.7a and CbmNav1.7b) revealed a novel loss-of-function mutation (C934R) at the extracellular linker between segments 5 and 6 of domain II. In addition, post-transcriptional modification events, such as alternative splicing and RNA editing, amended the gating properties and kinetic features of CbmNav1.7a(C934). These results provide molecular and functional characteristics of VGSCs in mammalian IHCs and their contributions to spontaneous physiological activity during cochlear maturation.

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Acknowledgements

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, and 81730028), the National Basic Research Development Program of China (SQ2017YFSF080012), and the Postdoctoral Science Foundation of China (2018M640407).

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Authors and Affiliations

  1. Department of Otolaryngology – Head and Neck Surgery, Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200125, China

    You Zhou, Xueling Wang & Hao Wu

  2. Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, 200125, China

    You Zhou, Xueling Wang & Hao Wu

  3. Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, 200125, China

    You Zhou, Xueling Wang & Hao Wu

  4. Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai, 200444, China

    Chenchen Xia, Manli Yin & Yonghua Ji

  5. Translational Institute for Cancer Pain, Xinhua Hospital Chongming Branch, Shanghai, 202150, China

    Yonghua Ji

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  1. You Zhou
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  2. Chenchen Xia
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  4. Xueling Wang
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Correspondence to Hao Wu or Yonghua Ji.

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Zhou, Y., Xia, C., Yin, M. et al. Distribution and Functional Characteristics of Voltage-Gated Sodium Channels in Immature Cochlear Hair Cells. Neurosci. Bull. 36, 49–65 (2020). https://doi.org/10.1007/s12264-019-00415-3

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  • DOI: https://doi.org/10.1007/s12264-019-00415-3

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