title: Prestin regulation and function in residual outer hair cells after noise-induced hearing loss.
abstract: The outer hair cell (OHC) motor protein prestin is necessary for electromotility, which drives cochlear amplification and produces exquisitely sharp frequency tuning. Tecta(C1509G) transgenic mice have hearing loss, and surprisingly have increased OHC prestin levels. We hypothesized, therefore, that prestin up-regulation may represent a generalized response to compensate for a state of hearing loss. In the present study, we sought to determine the effects of noise-induced hearing loss on prestin expression. After noise exposure, we performed cytocochleograms and observed OHC loss only in the basal region of the cochlea. Next, we patch clamped OHCs from the apical turn (9-12 kHz region), where no OHCs were lost, in noise-exposed and age-matched control mice. The non-linear capacitance was significantly higher in noise-exposed mice, consistent with higher functional prestin levels. We then measured prestin protein and mRNA levels in whole-cochlea specimens. Both Western blot and qPCR studies demonstrated increased prestin expression after noise exposure. Finally, we examined the effect of the prestin increase in vivo following noise damage. Immediately after noise exposure, ABR and DPOAE thresholds were elevated by 30-40 dB. While most of the temporary threshold shifts recovered within 3 days, there were additional improvements over the next month. However, DPOAE magnitudes, basilar membrane vibration, and CAP tuning curve measurements from the 9-12 kHz cochlear region demonstrated no differences between noise-exposed mice and control mice. Taken together, these data indicate that prestin is up-regulated by 32-58% in residual OHCs after noise exposure and that the prestin is functional. These findings are consistent with the notion that prestin increases in an attempt to partially compensate for reduced force production because of missing OHCs. However, in regions where there is no OHC loss, the cochlea is able to compensate for the excess prestin in order to maintain stable auditory thresholds and frequency discrimination.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California, United States of America.
authors.forename: Anping
authors.initials: A
authors.lastname: Xia
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California, United States of America.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California, United States of America.
authors.forename: Rosalie
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California, United States of America ; Department of Bioengineering, Rice University, Houston, Texas, United States of America.
authors.forename: Simon S
authors.initials: SS
authors.lastname: Gao
authors.affiliation: Bobby R. Alford Department of Otolaryngology - Head and Neck Surgery, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Will
authors.initials: W
authors.lastname: Clifton
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California, United States of America.
authors.forename: Patrick
authors.initials: P
authors.lastname: Raphael
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California, United States of America ; Department of Otolaryngology-Head and Neck Surgery, Chosun University, Gwangju, South Korea.
authors.forename: Sung-il
authors.initials: SI
authors.lastname: Chao
authors.affiliation: Bobby R. Alford Department of Otolaryngology - Head and Neck Surgery, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Fred A
authors.initials: FA
authors.lastname: Pereira
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, Texas, United States of America ; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America ; Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Groves
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California, United States of America.
authors.forename: John S
authors.initials: JS
authors.lastname: Oghalai
mesh_terms: D000818:Animals; D003055:Cochlear Microphonic Potentials; D016057:Evoked Potentials, Auditory, Brain Stem; D005786:Gene Expression Regulation; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism* / Q000473:pathology*; D006317:Hearing Loss, Noise-Induced / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008954:Models, Biological; D020409:Molecular Motor Proteins / Q000235:genetics / Q000378:metabolism*; D009622:Noise; D017084:Otoacoustic Emissions, Spontaneous; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D020409:Molecular Motor Proteins; C498720:Pres protein, mouse; D012333:RNA, Messenger