Developmental Alterations in the Distribution of Specific Lateral Wall Proteins Modify Outer Hair Cell Mechanical Properties
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Authors
Jensen-Smith, Heather Colleen
Issue Date
2006-01
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Dissertation
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en_US
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Abstract
In the mammalian cochlea, specialized outer hair cells (OHCs) housed within the organ of Corti exhibit nonlinear, mechanical responses to auditory stimulation [1]. These electromotile responses increase hearing sensitivity 100-fold (40 dB) and are responsible for frequency selectivity in the mammalian cochlea. OHC electromotile length change and force generation are essential for a sensitive and sharply-tuned cochlea. OHC stiffness is in turn important for effective transmission of force from OHCs to other cells in the organ of Corti. Maturation of stiffness in OHCs during development may therefore be an important factor in the onset and maturation of electromotility and hearing in mammals. The mechanical properties of developing and adult gerbil OHCs were compared using calibrated glass fibers. OHC compliance increased immediately before the onset of hearing. By the onset of hearing OHC compliance dramatically decreased.|Cochlear OHCs have a specialized lateral wall consisting of a plasma membrane, in which the motor protein prestin is densely packed, an actin-spectrin cortical lattice and subsurface cisternae. Developmental alterations in protein distribution and localization of each of these structures were correlated with alterations in OHC compliance to assess their potential to influence OHC mechanics before and after the onset of hearing. A reduction in lateral F-actin content was highly correlated with an increase in OHC compliance immediately before the onset of hearing. A large increase in prestin distribution at the onset of hearing was highly correlated with a decrease in compliance. These results suggest that F-actin and prestin modulate the passive mechanical properties of cochlear OHCs before and after the onset of hearing, respectively. Furthermore, these dramatic alterations in OHC mechanics clearly indicate that the mammalian OHC must acquire specific mechanical properties in concert with electromotility to generate a sharply tuned cochlea.
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Creighton University
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Thesis-Jensen-Smith.pdf