Kuni H. Iwasa, Ph.D.
Chief
Section on Biophysics
Laboratory of Cellular Biology
NIDCD/NIH
50 South Drive MSC 8027
Room 4–4152
Bethesda, MD 20892
Phone: (301) 496–3987
Fax: (301) 480–0827
E-mail: iwasa@nih.gov
Research Statement
The Section on Biophysics studies biophysical properties of sensory cells in the auditory and vestibular systems.
Recent Accomplishments
Of the properties of cochlear hair cells, the sensory cells in the ear that convert sound-induced mechanical vibration into electrical signal, reverse transduction, in which hair cells act as a motor, appears the most paradoxical. This function is essential for the sharp frequency discrimination by the ear because the tuning mechanism is based on mechanical resonance, which pumps energy into mechanical vibration. Mammalian outer hair cells have a voltage-dependent motor in the cell body. Non-mammals, which do not have outer hair cells, reverse transduction must be carried out by hair bundles. It has been shown that hair bundles can have negative stiffness. We have found that negative stiffness requires cooperative interactions between mechanotransducer channels in a hair bundle.
For clarifying the mechanism of the membrane motor in outer hair cells, we have been testing our hypothesis called the "area motor model." This model proposes that the hair cell motor has an electric charge that is transferable across the membrane and that charge transfer is coupled with changes in the membrane area of the motor. We found such a mechanism theoretically belongs to a class of piezoelectricity in that energy conversion is direct and reciprocal. Namely, the motor converts mechanical energy back into electrical energy in a symmetric manner. We experimentally showed that the piezoelectric reciprocity is satisfied, demonstrating the piezoelectric nature of the motor.
Force produced by outer hair cells depends on the voltage oscillation (receptor potential) in the cells due to transducer current in hair bundles. Studies on the electric properties of these cells indicate that the receptor potential is highly attenuated by the hair cell's intrinsic electric circuit (RC filter). As the result, receptor potential appeared too small to affect vibration in the cochlea. This is known as the RC time constant problem. We found that the receptor potential at the resonance frequency is not heavily attenuated up to 10 kHz because piezoelectric resonance can overcome the cells' RC filter. The frequency limit arises from the condition because that force produced by outer hair cells needs to cancel out viscous drag. For frequencies higher than 10 kHz, we expect that fast potassium channels enhance the receptor potential.
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Lab Personnel
Ghanshyam Sinha (Send e-mail)
Jie Fang (Send e-mail)
Bora Sul (Send e-mail)
Selected Publications
- Fang, J., Sakata, T., Marriott, G., and Iwasa, K. H. Probing conformational changes of prestin with thiol-reactive optical switches. Biophys. J. (2008) in press.
- Iwasa, K. H. and Sul. B., Effect of the cochlear microphonic on the limiting frequency of the mammalian ear. J. Acoust. Soc. Am. (2008) in press.
- Fang, J. and Iwasa, K. H. Effects of chlorpromazine and trinitrophenol on the membrane motor of outer hair cells. Biophys. J. (2007) 93: 1809-1817
- Dong XX, Iwasa KH. Tension sensitivity of prestin: comparison with the membrane motor in outer hair cells. Biophysical Journal 86(2):1201–8, 2004.
- Ospeck M, Dong XX, Iwasa KH. Limiting frequency of the cochlear amplifier based on electromotility of outer hair cells. Biophysical Journal 84(2 Pt 1):739–749, 2003.
- Dong XX, Ospeck M, Iwasa KH. Piezoelectric reciprocal relationship of the membrane motor in the cochlear outer hair cell. Biophysical Journal 82(3):1254–1259, 2002.
- Iwasa KH. A two-state piezoelectric model for outer hair cell motility. Biophysical Journal 81(5):2495–2506, 2001.
- Dong XX, Ehrenstein D, Iwasa KH. Fluctuation of motor charge in the lateral membrane of the cochlear outer hair cell. Biophysical Journal 79():1876–1882, 2000.
- Adachi M, Iwasa KH. Electrically driven motor in the outer hair cell: effect of a mechanical constraint. Proceedings of the National Academy of Sciences of the United States of America 96(13):7244–9, 1999.
- Iwasa KH. Current noise spectrum and capacitance due to the membrane motor in the outer hair cell membrane theory. Biophysical Journal 73:2965–2971, 1997.
- Adachi M, Iwasa KH. Effect of diamide on force generation and axial stiffness of the cochlear outer hair cell. Biophysical Journal 73:2809–2818, 1997.
- Iwasa KH, Adachi M. Force generation in the outer hair cell of the cochlea. Biophysical Journal 73:546–555, 1997.
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