Piezo1 haploinsufficiency does not alter mechanotransduction in mouse cochlear outer hair cells.

Laura F Corns,Walter Marcotti

doi:10.14814/phy2.12701

Abstract

The mechanoelectrical transducer (MET) channels located at the stereocilia tip of cochlear hair cells are crucial to convert the mechanical energy of sound into receptor potentials, but the identity of its pore-forming subunits remains uncertain. Piezo1, which has been identified in the transcriptome of mammalian cochlear hair cells, encodes a transmembrane protein that forms mechanosensitive channels in other tissues. We investigated the properties of the MET channel in outer hair cells (OHCs) of Piezo1 mice (postnatal day 6-9). The MET current was elicited by deflecting the hair bundle of OHCs using sinewave and step stimuli from a piezo-driven fluid jet. Apical and basal OHCs were investigated because the properties of the MET channel vary along the cochlea. We found that the maximal MET current amplitude and the resting open probability of the MET channel in OHCs were similar between Piezo1(+/-) haploinsufficient mice and wild-type littermates. The sensitivity to block by the permeant MET channel blocker dihydrostreptomycin was also similar between the two genotypes. Finally, the anomalous mechano-gated current, which is activated by sheer force and which is tip-link independent, was unaffected in OHCs from Piezo1(+/-) haploinsufficient mice. Our results suggest that Piezo1 isunlikely to be a component of the MET channel complex in mammalian cochlear OHCs.

Highlights

The hair cells of the organ of Corti within the mammalian cochlea convert mechanical stimuli into receptor potentials
The absence of a hearing phenotype would not preclude the involvement of Piezo1 in mechano-electrical transduction since, for example, the loss of TMC2 does not confer hearing loss despite affecting the mechanoelectrical transducer (MET) current in the immature cochlear hair cells (Kawashima et al 2011)
To investigate the possible involvement of Piezo1 in hair cells, MET currents in apical and basal outer hair cells (OHCs) were elicited by displacing stereociliary hair bundles with sinewave stimuli from a piezoelectric fluid jet

Summary

Introduction

The hair cells of the organ of Corti within the mammalian cochlea convert mechanical stimuli into receptor potentials. The mechanoelectrical transducer (MET) channel complex, which allows the influx of positive ions into the hair cells, resides in the region where the tip link inserts into the tip of the lower stereocilia (Beurg et al 2009). While TMHS/LHFPL5 and TMIE are unlikely to form the pore-forming subunits of the MET channel (Xiong et al 2012; Zhao et al 2014), mutations in tmc and tmc have been shown to affect the MET channel (Kawashima et al 2011; Pan et al 2013; Corns et al 2016). The possibility that other proteins could be contributing to the MET channel pore in hair cells has been suggested by the fact that an anomalous MET current, which is independent of tiplinks and is instead evoked by sheer stress (Marcotti et al 2014), has been shown to be present in mice lacking both TMC1 and TMC2 (Beurg et al 2014)

Methods

Results

Conclusion