The outer hair cell, one of the two mechanoreceptor cells in the cochlea, has motility. It is a critical factor for the frequency specificity and for the wide dynamic range of the mammalian ear. Because a mechanosensory cell with motility can exert force responding to mechanical vibration, it can modulate the vibration in the inner ear. For this reason it has been assumed essential for the cell's biological function. The goal of this project is to elucidate the mechanism of this motility. We have been testing our hypothesis that the motor has a charge transferable across the membrane and that charge transfer is coupled with changes in the membrane area of the motor, realizing direct conversion of electrical energy into mechanical energy. This model predicts voltage and tension dependence of charge transfer, which we experimentally confirmed. We further showed that constraint on the membrane area drastically reduces charge transfer. This observation demonstrates that the motile mechanism resides in the membrane and that it is indeed based on membrane area changes tightly coupled with charge transfer. It was recently shown that the axial stiffness of this cylindrical cell depends on the membrane potential. We showed that the observation is consistent with the model which does not assume stiffness changes in any of its components. That is because the axial stiffness is reduced by conformational transitions of the motor, which depends on both the membrane potential and tension. To clarify the effect of the motile activity of the outer hair cell in the ear, we determined force generation by the cell. The value for isometric force is about 0.1 nN/mV, which agrees with the prediction of the model. To determine the speed of the motile mechanism, we recently examined the frequency spectrum of membrane current noise due to flipping of motor charges. The spectrum is high pass as expected and has the characteristic frequency of about 30 kHz, indicating that is the speed of conformational transitions of the motor. This frequency exceeds 20 kHz, the higher end of the auditory range. These efforts should lead to further clarification of the motility of the outer hair cell and its biological role.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Intramural Research (Z01)
Project #
1Z01DC000010-09
Application #
6431969
Study Section
(LCB)
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2000
Total Cost
Indirect Cost
Name
Deafness & Other Communication Disorders
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Sul, Bora; Iwasa, Kuni H (2009) Amplifying effect of a release mechanism for fast adaptation in the hair bundle. J Acoust Soc Am 126:4-6
Fang, Jie; Iwasa, K H (2007) Effects of chlorpromazine and trinitrophenol on the membrane motor of outer hair cells. Biophys J 93:1809-17
Fang, Jie; Iwasa, K H (2006) Effects of tarantula toxin GsMTx4 on the membrane motor of outer hair cells. Neurosci Lett 404:213-6
Ospeck, Mark; Dong, Xiao-Xia; Fang, Jie et al. (2006) Electromotility in outer hair cells: a supporting role for fast potassium conductance. ORL J Otorhinolaryngol Relat Spec 68:373-7
Dong, X-X; Iwasa, K H (2004) Tension sensitivity of prestin: comparison with the membrane motor in outer hair cells. Biophys J 86:1201-8
Ospeck, Mark; Dong, Xiao-xia; Iwasa, Kuni H (2003) Limiting frequency of the cochlear amplifier based on electromotility of outer hair cells. Biophys J 84:739-49
Iwasa, K H; Ehrenstein, G (2002) Cooperative interaction as the physical basis of the negative stiffness in hair cell stereocilia. J Acoust Soc Am 111:2208-12
Dong, Xiao-xia; Ospeck, Mark; Iwasa, Kuni H (2002) Piezoelectric reciprocal relationship of the membrane motor in the cochlear outer hair cell. Biophys J 82:1254-9
Iwasa, K H (2001) A two-state piezoelectric model for outer hair cell motility. Biophys J 81:2495-506
Kakehata, S; Dallos, P; Brownell, W E et al. (2000) Current concept of outer hair cell motility. Auris Nasus Larynx 27:349-55

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