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

A. Catalina Vélez-Ortega, Mary J. Freeman, Artur A. Indzhykulian, Jonathan M. Grossheim, Gregory I. Frolenkov

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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.

Original languageEnglish
Article numbere24661
JournaleLife
Volume6
DOIs
StatePublished - Mar 28 2017

Bibliographical note

Funding Information:
We thank Dr. James R Bartles and Dr. Lili Zheng for valuable comments and productive discussions, as well as for their efforts to reproduce the observed phenomena in an in vitro system. This study was supported by NIDCD/NIH (R01 DC014658 and R01 DC008861 to GIF) and American Hearing Research Foundation (to ACV).

Publisher Copyright:
© Vélez-Ortega et al.

ASJC Scopus subject areas

  • Neuroscience (all)
  • Biochemistry, Genetics and Molecular Biology (all)
  • Immunology and Microbiology (all)

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