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