The mammalian ear contains two types of sensory receptor cells, inner hair cells (IHC) and outer hair cells (OHC). IHCs communicate auditory information to the brain, whereas OHCs function as local amplifiers to boost the input to IHCs. Without functioning OHCs, hearing threshold is severely degraded and selectivity to different sound frequencies is effectively eliminated. How OHCs boost the ear's response is one of the central issues of hearing science. There are two competing theories. In one, it is assumed that the input organelles of hair cells, so called stereocilia, are motile and feed energy back to the vibrating system in which they are embedded, thereby boosting the response. The other theory is based on the observation that OHCs change their length in response to changes in their electrical state. These length changes are mediated by a novel molecular motor, prestin, which we identified five years ago. Both theories have some experimental support and both have weaknesses. It is the principal aim of the present work to establish the mode of amplification by OHCs and thereby reconcile the two theories, The primary means of accomplishing this is to study the physiological behavior of mice engineered to express mutated forms of prestin. In other words, we examine response characteristics of animals that have the molecule prestin in their OHCs, but the molecule is non-functional. Thereby, these animals do not have motile OHCs and, consequently, one of the proposed means of amplification is absent, while the other is unaltered. Additional experiments are designed to examine the molecular nature of prestin, which may be the key molecule in mammalian hearing. Hearing loss and deafness, congenital or acquired during life, and especially prevalent in our aging population, represent one of the most common public health problems. A very significant fraction of these deficits involve deterioration or death of hair cells, especially OHCs. Our entire effort is focused on unreveling the properties of OHCs and their unique function in the hearing process.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC000089-39
Application #
7590394
Study Section
Auditory System Study Section (AUD)
Program Officer
Freeman, Nancy
Project Start
1991-01-01
Project End
2011-03-31
Budget Start
2009-04-01
Budget End
2010-03-31
Support Year
39
Fiscal Year
2009
Total Cost
$574,411
Indirect Cost
Name
Northwestern University at Chicago
Department
Other Health Professions
Type
Schools of Arts and Sciences
DUNS #
160079455
City
Evanston
State
IL
Country
United States
Zip Code
60201
Wiwatpanit, Teerawat; Lorenzen, Sarah M; CantĂș, Jorge A et al. (2018) Trans-differentiation of outer hair cells into inner hair cells in the absence of INSM1. Nature 563:691-695
Takahashi, Satoe; Sun, Willy; Zhou, Yingjie et al. (2018) Prestin Contributes to Membrane Compartmentalization and Is Required for Normal Innervation of Outer Hair Cells. Front Cell Neurosci 12:211
Wiwatpanit, Teerawat; Remis, Natalie N; Ahmad, Aisha et al. (2018) Codeficiency of Lysosomal Mucolipins 3 and 1 in Cochlear Hair Cells Diminishes Outer Hair Cell Longevity and Accelerates Age-Related Hearing Loss. J Neurosci 38:3177-3189
Xu, Yingyue; Cheatham, Mary Ann; Siegel, Jonathan H (2017) Identifying the Origin of Effects of Contralateral Noise on Transient Evoked Otoacoustic Emissions in Unanesthetized Mice. J Assoc Res Otolaryngol 18:543-553
Takahashi, Satoe; Cheatham, Mary Ann; Zheng, Jing et al. (2016) The R130S mutation significantly affects the function of prestin, the outer hair cell motor protein. J Mol Med (Berl) 94:1053-62
Cheatham, Mary Ann; Ahmad, Aisha; Zhou, Yingjie et al. (2016) Increased Spontaneous Otoacoustic Emissions in Mice with a Detached Tectorial Membrane. J Assoc Res Otolaryngol 17:81-8
Takahashi, Satoe; Homma, Kazuaki; Zhou, Yingjie et al. (2016) Susceptibility of outer hair cells to cholesterol chelator 2-hydroxypropyl-?-cyclodextrine is prestin-dependent. Sci Rep 6:21973
Cheatham, Mary Ann; Edge, Roxanne M; Homma, Kazuaki et al. (2015) Prestin-Dependence of Outer Hair Cell Survival and Partial Rescue of Outer Hair Cell Loss in PrestinV499G/Y501H Knockin Mice. PLoS One 10:e0145428
Keller, Jacob Pearson; Homma, Kazuaki; Duan, Chongwen et al. (2014) Functional regulation of the SLC26-family protein prestin by calcium/calmodulin. J Neurosci 34:1325-32
Homma, Kazuaki; Duan, Chongwen; Zheng, Jing et al. (2013) The V499G/Y501H mutation impairs fast motor kinetics of prestin and has significance for defining functional independence of individual prestin subunits. J Biol Chem 288:2452-63

Showing the most recent 10 out of 31 publications