Mechanotransduction is required for establishing and maintaining mature inner hair cells and regulating efferent innervation

Laura F Corns,Saaid Safieddine,Federico Ceriani,Walter Marcotti,Aenea Hendry,Corné J Kros,Christine Petit,Stuart L Johnson,Karen P Steel,Andy Forge,Kishani M Ranatunga,David N Furness,Terri Roberts

doi:10.1038/s41467-018-06307-w

Laura F Corns, Saaid Safieddine + Show 11 more

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https://doi.org/10.1038/s41467-018-06307-w

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In the adult auditory organ, mechanoelectrical transducer (MET) channels are essential for transducing acoustic stimuli into electrical signals. In the absence of incoming sound, a fraction of the MET channels on top of the sensory hair cells are open, resulting in a sustained depolarizing current. By genetically manipulating the in vivo expression of molecular components of the MET apparatus, we show that during pre-hearing stages the MET current is essential for establishing the electrophysiological properties of mature inner hair cells (IHCs). If the MET current is abolished in adult IHCs, they revert into cells showing electrical and morphological features characteristic of pre-hearing IHCs, including the re-establishment of cholinergic efferent innervation. The MET current is thus critical for the maintenance of the functional properties of adult IHCs, implying a degree of plasticity in the mature auditory system in response to the absence of normal transduction of acoustic signals.

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In the adult auditory organ, mechanoelectrical transducer (MET) channels are essential for transducing acoustic stimuli into electrical signals
We found that IK,f was present in adult control inner hair cells (IHCs) (Pcdh15+/av3J: Fig. 1a, 3.8 ± 0.5 nA at −25 mV, n = 10, mean ± Scanning electron microscopy (SEM); see Methods for details) but absent in Pcdh15av3J/av3J mutant mice (Fig. 1b)
Here we show that the MET current is essential to establish and maintain the key biophysical and morphological properties characteristic of adult IHCs

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Introduction

In the adult auditory organ, mechanoelectrical transducer (MET) channels are essential for transducing acoustic stimuli into electrical signals. Hair bundle displacement causes the opening of mechanoelectrical transducer (MET) channels located at the tips of the shorter and middle rows of stereocilia, and the transduction of acoustic information into a receptor potential inside the hair cells. The endolymph that surrounds the hair bundle has a low Ca2+ concentration in both pre-hearing (second post-natal week: ~ 300 μM)[5] and adult (~ 20–40 μM)[6] cochleae, resulting in a larger in vivo resting open probability of the MET channel. In the immature cochlea, the functional MET channels together with the maturing endocochlear potential[7] and endolymphatic Ca2+ concentration[5], trigger the developmental switch from spiking IHCs to high-frequency signal transducers. The loss of the MET current in adult IHCs causes them to revert to an immature, pre-hearing phenotype and they re-acquire efferent innervation

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