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Variable number of TMC1-dependent mechanotransducer channels underlie tonotopic conductance gradients in the cochlea

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  • Maryline Beurg

    (University of Wisconsin School of Medicine and Public Health)

  • Runjia Cui

    (National Institutes of Health)

  • Adam C. Goldring

    (University of Wisconsin School of Medicine and Public Health)

  • Seham Ebrahim

    (National Institutes of Health)

  • Robert Fettiplace

    (University of Wisconsin School of Medicine and Public Health)

  • Bechara Kachar

    (National Institutes of Health)

Abstract

Functional mechanoelectrical transduction (MET) channels of cochlear hair cells require the presence of transmembrane channel-like protein isoforms TMC1 or TMC2. We show that TMCs are required for normal stereociliary bundle development and distinctively influence channel properties. TMC1-dependent channels have larger single-channel conductance and in outer hair cells (OHCs) support a tonotopic apex-to-base conductance gradient. Each MET channel complex exhibits multiple conductance states in ~50 pS increments, basal MET channels having more large-conductance levels. Using mice expressing fluorescently tagged TMCs, we show a three-fold increase in number of TMC1 molecules per stereocilium tip from cochlear apex to base, mirroring the channel conductance gradient in OHCs. Single-molecule photobleaching indicates the number of TMC1 molecules per MET complex changes from ~8 at the apex to ~20 at base. The results suggest there are varying numbers of channels per MET complex, each requiring multiple TMC1 molecules, and together operating in a coordinated or cooperative manner.

Suggested Citation

  • Maryline Beurg & Runjia Cui & Adam C. Goldring & Seham Ebrahim & Robert Fettiplace & Bechara Kachar, 2018. "Variable number of TMC1-dependent mechanotransducer channels underlie tonotopic conductance gradients in the cochlea," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04589-8
    DOI: 10.1038/s41467-018-04589-8
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    Cited by:

    1. Jeong Han Lee & Maria C. Perez-Flores & Seojin Park & Hyo Jeong Kim & Yingying Chen & Mincheol Kang & Jennifer Kersigo & Jinsil Choi & Phung N. Thai & Ryan L. Woltz & Dolores Columba Perez-Flores & Gu, 2024. "The Piezo channel is a mechano-sensitive complex component in the mammalian inner ear hair cell," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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