Activity-dependent regulation of prestin expression in mouse outer hair cells

Author:

Song Yohan1,Xia Anping1,Lee Hee Yoon1,Wang Rosalie1,Ricci Anthony J.1,Oghalai John S.1

Affiliation:

1. Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California

Abstract

Prestin is a membrane protein necessary for outer hair cell (OHC) electromotility and normal hearing. Its regulatory mechanisms are unknown. Several mouse models of hearing loss demonstrate increased prestin, inspiring us to investigate how hearing loss might feedback onto OHCs. To test whether centrally mediated feedback regulates prestin, we developed a novel model of inner hair cell loss. Injection of diphtheria toxin (DT) into adult CBA mice produced significant loss of inner hair cells without affecting OHCs. Thus, DT-injected mice were deaf because they had no afferent auditory input despite OHCs continuing to receive normal auditory mechanical stimulation and having normal function. Patch-clamp experiments demonstrated no change in OHC prestin, indicating that loss of information transfer centrally did not alter prestin expression. To test whether local mechanical feedback regulates prestin, we used TectaC1509G mice, where the tectorial membrane is malformed and only some OHCs are stimulated. OHCs connected to the tectorial membrane had normal prestin levels, whereas OHCs not connected to the tectorial membrane had elevated prestin levels, supporting an activity-dependent model. To test whether the endocochlear potential was necessary for prestin regulation, we studied TectaC1509G mice at different developmental ages. OHCs not connected to the tectorial membrane had lower than normal prestin levels before the onset of the endocochlear potential and higher than normal prestin levels after the onset of the endocochlear potential. Taken together, these data indicate that OHC prestin levels are regulated through local feedback that requires mechanoelectrical transduction currents. This adaptation may serve to compensate for variations in the local mechanical environment.

Funder

DOD | Congressionally Directed Medical Research Programs (CDMRP)

HHS | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD)

Howard Hughes Medical Institute (HHMI)

stanford society for physician scholars

Publisher

American Physiological Society

Subject

Physiology,General Neuroscience

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