TMC1 is an essential component of a leak channel that modulates tonotopy and excitability of auditory hair cells in mice

  1. Shuang Liu
  2. Shufeng Wang
  3. Linzhi Zou
  4. Jie Li
  5. Chenmeng Song
  6. Jiaofeng Chen
  7. Qun Hu
  8. Lian Liu
  9. Pingbo Huang
  10. Wei Xiong  Is a corresponding author
  1. Tsinghua University, China
  2. Hong Kong University of Science and Technology, Hong Kong

Abstract

Hearing sensation relies on the mechano-electrical transducer (MET) channel of cochlear hair cells, in which transmembrane channel-like 1 (TMC1) and transmembrane channel-like 2 (TMC2) have been proposed to be the pore-forming subunits in mammals. TMCs were also found to regulate other biological processes than MET in invertebrates ranging from sensations to motor function. However, whether TMCs have a non-MET role remains elusive in mammals. Here, we report that in mouse hair cells, TMC1, but not TMC2, provides a background leak conductance, with properties distinct from those of the MET channels. By cysteine substitutions in TMC1, we characterized 4 amino acids that are required for the leak conductance. The leak conductance is graded in frequency-dependent manner along the length of the cochlea and indispensable for action potential firing. Taken together, our results show that TMC1 confers a background leak conductance in cochlear hair cells, which may be critical for the acquisition of sound-frequency and -intensity.

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All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Shuang Liu

    School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Shufeng Wang

    School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Linzhi Zou

    School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Jie Li

    School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Chenmeng Song

    School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Jiaofeng Chen

    School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Qun Hu

    School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Lian Liu

    School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Pingbo Huang

    Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4560-8760
  10. Wei Xiong

    School of Life Sciences, Tsinghua University, Beijing, China
    For correspondence
    wei_xiong@tsinghua.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2784-7696

Funding

National Natural Science Foundation of China (31522025)

  • Wei Xiong

Beijing Municipal Science & Technology Commission (Z181100001518001)

  • Wei Xiong

Hong Kong University of Science and Technology (N_HKUST614/18)

  • Pingbo Huang

National Natural Science Foundation of China (31571080)

  • Wei Xiong

National Natural Science Foundation of China (81873703)

  • Wei Xiong

National Natural Science Foundation of China (3181101148)

  • Wei Xiong

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The experimental procedures on mice were approved by the Institutional Animal Care and Use Committee of Tsinghua University.(Animal Protocol # : 15 XW1 )

Reviewing Editor

  1. Dwight E Bergles, Johns Hopkins University School of Medicine, United States

Version history

  1. Received: April 5, 2019
  2. Accepted: October 24, 2019
  3. Accepted Manuscript published: October 29, 2019 (version 1)
  4. Version of Record published: November 13, 2019 (version 2)

Copyright

© 2019, Liu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Shuang Liu
  2. Shufeng Wang
  3. Linzhi Zou
  4. Jie Li
  5. Chenmeng Song
  6. Jiaofeng Chen
  7. Qun Hu
  8. Lian Liu
  9. Pingbo Huang
  10. Wei Xiong
(2019)
TMC1 is an essential component of a leak channel that modulates tonotopy and excitability of auditory hair cells in mice
eLife 8:e47441.
https://doi.org/10.7554/eLife.47441

Share this article

https://doi.org/10.7554/eLife.47441

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