1. Cell Biology
  2. Neuroscience
Download icon

Mechanotransduction current is essential for stability of the transducing stereocilia in mammalian auditory hair cells

  1. A Catalina Vélez-Ortega
  2. Mary J Freeman
  3. Artur A Indzhykulian
  4. Jonathan M Grossheim
  5. Gregory I Frolenkov  Is a corresponding author
  1. College of Medicine, University of Kentucky, United States
  2. Harvard Medical School, United States
Research Article
  • Cited 25
  • Views 2,269
  • Annotations
Cite this article as: eLife 2017;6:e24661 doi: 10.7554/eLife.24661

Abstract

Mechanotransducer channels at the tips of sensory stereocilia of inner ear hair cells are gated by the tension of 'tip links' interconnecting stereocilia. To ensure maximal sensitivity, tip links are tensioned at rest, resulting in a continuous influx of Ca2+ into the cell. Here we show that this constitutive Ca2+ influx, usually considered as potentially deleterious for hair cells, is in fact essential for stereocilia stability. In the auditory hair cells of young postnatal mice and rats, a reduction in mechanotransducer current, via pharmacological channel blockers or disruption of tip links, leads to stereocilia shape changes and shortening. These effects occur only in stereocilia that harbor mechanotransducer channels, recover upon blocker washout or tip link regeneration, and can be replicated by manipulations of extracellular Ca2+ or intracellular Ca2+ buffering. Thus, our data provide the first experimental evidence for the dynamic control of stereocilia morphology by the mechanotransduction current.

Article and author information

Author details

  1. A Catalina Vélez-Ortega

    Department of Physiology, College of Medicine, University of Kentucky, Lexington, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9157-8390
  2. Mary J Freeman

    Department of Physiology, College of Medicine, University of Kentucky, Lexington, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Artur A Indzhykulian

    Department of Neurobiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jonathan M Grossheim

    Department of Physiology, College of Medicine, University of Kentucky, Lexington, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Gregory I Frolenkov

    Department of Physiology, College of Medicine, University of Kentucky, Lexington, United States
    For correspondence
    Gregory.Frolenkov@uky.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9810-5024

Funding

National Institute on Deafness and Other Communication Disorders (DC014658)

  • Gregory I Frolenkov

National Institute on Deafness and Other Communication Disorders (DC008861)

  • Gregory I Frolenkov

American Hearing Research Foundation

  • A Catalina Vélez-Ortega

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animal procedures were approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Kentucky (protocol 00903M2005).

Reviewing Editor

  1. Jeremy Nathans, Johns Hopkins University School of Medicine, United States

Publication history

  1. Received: December 24, 2016
  2. Accepted: March 27, 2017
  3. Accepted Manuscript published: March 28, 2017 (version 1)
  4. Version of Record published: April 27, 2017 (version 2)

Copyright

© 2017, Vélez-Ortega 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

  • 2,269
    Page views
  • 509
    Downloads
  • 25
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

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)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Cell Biology
    2. Developmental Biology
    Moran Cohen-Berkman et al.
    Research Article Updated
    1. Biochemistry and Chemical Biology
    2. Cell Biology
    Andrea Ruiz-Velasco et al.
    Research Article Updated