Sensory receptor cells of the mammalian cochlea are morphologically and functionally dichotomized. Inner hair cells (IHCs) transmit auditory information to the brain, while outer hair cells (OHCs) amplify the mechanical signal, which is then transduced by IHCs. Both types of the hair cells respond to basilar membrane (BM) vibration by producing a transducer current through mechanotransducer channels located at the tip of the stereocilia when their hair bundles are deflected. The receptor potential generated by IHCs facilitates the release of neurotransmitters at their synaptic end. The receptor potential produced by OHCs, however, provides the input to their motor activity. Somatic motility of OHCs is generally thought to be responsible for the cochlear amplification in mammals. OHCs are innervated predominantly by efferent fibers originated in the brainstem. The effect of efferent action, mediated by the release of ACh, can alter micromechanical events within the cochlear partition and thereby provides a 'gain control'of the cochlear amplifier. The long-term goal of our laboratory is to study OHC motility, hair cell mechanoelectric transduction, and the mechanisms underlying the mechanical amplification. Specifically, our aims are: 1) to study the mechanical properties of OHCs in wild-type and prestin-mutant mice;2) to study the effects of efferent activation by electrical stimulation on receptor currents and receptor potentials of the OHCs;3) to study mechanoelectric transduction of adult IHCs. Isolated mouse OHCs will be used for Aim 1, while gerbil hemicochlea preparations will be used for Aim 2, and Aim 3. The hemicochlea preparation will allow us to measure hair cell receptor currents (or receptor potentials) and BM motion simultaneously at various cochlear locations while the BM is mechanically stimulated and/or the efferent terminals are electrically stimulated. Studying the mechanoelectrical and electromechanical transduction of hair cells will delineate the function of the sensory cells in hearing. Because the majority of Americans with hearing loss, some 30 millions in all,have some kind of hair cell damage, understanding the operation of hair cells is essential to the biological remediation and prevention of hair cell-related hearing loss and deafness.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC004696-11
Application #
7991355
Study Section
Auditory System Study Section (AUD)
Program Officer
Freeman, Nancy
Project Start
2001-01-15
Project End
2011-12-11
Budget Start
2010-12-01
Budget End
2011-12-11
Support Year
11
Fiscal Year
2011
Total Cost
$288,429
Indirect Cost
Name
Creighton University
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
053309332
City
Omaha
State
NE
Country
United States
Zip Code
68178
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Lovas, Sándor; He, David Z Z; Liu, Huizhan et al. (2015) Glutamate transporter homolog-based model predicts that anion-π interaction is the mechanism for the voltage-dependent response of prestin. J Biol Chem 290:24326-39
Li, Yi; Liu, Huizhan; Li, Jun et al. (2014) Morphology and ciliary motion of mucosa in the Eustachian tube of neonatal and adult gerbils. PLoS One 9:e99840
Zhang, Qian; Liu, Huizhan; Soukup, Garrett A et al. (2014) Identifying microRNAs involved in aging of the lateral wall of the cochlear duct. PLoS One 9:e112857
Liu, Huizhan; Pecka, Jason L; Zhang, Qian et al. (2014) Characterization of transcriptomes of cochlear inner and outer hair cells. J Neurosci 34:11085-95
He, David Z Z; Lovas, Sandor; Ai, Yu et al. (2014) Prestin at year 14: progress and prospect. Hear Res 311:25-35
Zhang, Qian; Liu, Huizhan; McGee, Joann et al. (2013) Identifying microRNAs involved in degeneration of the organ of corti during age-related hearing loss. PLoS One 8:e62786
Tang, Jie; Pecka, Jason L; Fritzsch, Bernd et al. (2013) Lizard and frog prestin: evolutionary insight into functional changes. PLoS One 8:e54388
Mao, Zhongping; Zhao, Lijun; Pu, Lichun et al. (2013) How well can centenarians hear? PLoS One 8:e65565
Tan, Xiaodong; Pecka, Jason L; Tang, Jie et al. (2012) A motif of eleven amino acids is a structural adaptation that facilitates motor capability of eutherian prestin. J Cell Sci 125:1039-47

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