TMC1 is an essential component of a leak channel that modulates tonotopy and excitability of auditory hair cells in mice
- Tsinghua University, China
- 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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
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 )
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.
Metrics
-
- 2,878
- views
-
- 455
- downloads
-
- 27
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
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
