The mechanoelectrical transducer channel is not required for regulation of cochlear blood flow during loud sound exposure in mice

George W S Burwood,Jianlong Yang,Sarah Foster,Teresa Wilson,Sean Elkins,Alfred L Nuttall,Gangjun Liu,Yuan Zhang,Suzan Dziennis

doi:10.1038/s41598-020-66192-6

Abstract

The mammalian cochlea possesses unique acoustic sensitivity due to a mechanoelectrical ‘amplifier’, which requires the metabolic support of the cochlear lateral wall. Loud sound exposure sufficient to induce permanent hearing damage causes cochlear blood flow reduction, which may contribute to hearing loss. However, sensory epithelium involvement in the cochlear blood flow regulation pathway is not fully described. We hypothesize that genetic manipulation of the mechanoelectrical transducer complex will abolish sound induced cochlear blood flow regulation. We used salsa mice, a Chd23 mutant with no mechanoelectrical transduction, and deafness before p56. Using optical coherence tomography angiography, we measured the cochlear blood flow of salsa and wild-type mice in response to loud sound (120 dB SPL, 30 minutes low-pass filtered noise). An expected sound induced decrease in cochlear blood flow occurred in CBA/CaJ mice, but surprisingly the same sound protocol induced cochlear blood flow increases in salsa mice. Blood flow did not change in the contralateral ear. Disruption of the sympathetic nervous system partially abolished the observed wild-type blood flow decrease but not the salsa increase. Therefore sympathetic activation contributes to sound induced reduction of cochlear blood flow. Additionally a local, non-sensory pathway, potentially therapeutically targetable, must exist for cochlear blood flow regulation.

Highlights

The mammalian cochlea possesses unique acoustic sensitivity due to a mechanoelectrical ‘amplifier’, which requires the metabolic support of the cochlear lateral wall
Www.nature.com/scientificreports systems rely upon activation of the sensory hair cells which contain sound activated mechanoelectrical transducer (MET) channels. It is the aim of this study to reveal whether the MET channel is required for cochlear blood flow regulation
To confirm that MET channel activity was abolished in our backcrossed salsa mice at 7–8 weeks of age, we screened their hearing with Auditory brainstem response (ABR) and 2f1-f2 Distortion product otoacoustic emission (DPOAE)

Summary

Introduction

The mammalian cochlea possesses unique acoustic sensitivity due to a mechanoelectrical ‘amplifier’, which requires the metabolic support of the cochlear lateral wall. We assume that due to their tight coupling to acoustic stimulation, both systems rely upon activation of the sensory hair cells which contain sound activated mechanoelectrical transducer (MET) channels It is the aim of this study to reveal whether the MET channel is required for cochlear blood flow regulation. Salsa mice express a point mutation in a Ca2+-binding motif of cadherin[23] (Cdh23), a vital component of normal tip links, which facilitate activation of the MET channel when sound stimulates the hair cells[12] These mice show progressive tip-link loss, and eventual organ of Corti degeneration, rendering these animals profoundly deaf. We reasoned that if the MET channel is required for regulation of cochlear blood flow, the lateral wall blood flow of salsa mice will not change in response to loud sound exposure, in comparison to control. We present evidence to suggest that the MET channel is required for the interaction between sympathetic neural mechanisms and the cochlea, but not for local control of cochlear blood flow

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Conclusion