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

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

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.

Highlights

The sense of hearing depends on stereocilia, the microvilli-like mechanosensory projections at the apical surface of inner ear hair cells
In our previous study (Indzhykulian et al, 2013), we noticed relatively slow changes of the stereocilia tip shape after breaking the tip links. We observed these changes in scanning electron microscopy (SEM) images obtained from samples fixed at different time points after tip link breakage
Our study provides the first experimental evidence for the role of the mechano-electrical transduction (MET) current in the maintenance of hair bundle structural stability in mammalian auditory hair cells

Summary

Introduction

The sense of hearing depends on stereocilia, the microvilli-like mechanosensory projections at the apical surface of inner ear hair cells. Soundinduced deflections of a hair bundle modulate the tension of the tip links, which controls the opening of mechano-electrical transduction (MET) channels (Assad et al, 1991) These channels are located at the tips of shorter but not the tallest row stereocilia (Beurg et al, 2009). The resting tip link tension increases the open probability of MET channels, resulting in a continuous influx of Ca2+ into the cell through these non-selective cation channels (Corey and Hudspeth, 1979). This constitutive Ca2+ influx is perceived as a potentially deleterious consequence of the extreme sensitivity of the MET apparatus in the auditory hair

Methods

Results

Conclusion