Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier

Nature volume 419, pages 300–304 (2002)Cite this article

Abstract

Hearing sensitivity in mammals is enhanced by more than 40 dB (that is, 100-fold) by mechanical amplification thought to be generated by one class of cochlear sensory cells, the outer hair cells1,2,3,4. In addition to the mechano-electrical transduction required for auditory sensation, mammalian outer hair cells also perform electromechanical transduction, whereby transmembrane voltage drives cellular length changes at audio frequencies in vitro5,6,7. This electromotility is thought to arise through voltage-gated conformational changes in a membrane protein8,9, and prestin has been proposed as this molecular motor10,11,12. Here we show that targeted deletion of prestin in mice results in loss of outer hair cell electromotility in vitro and a 40–60 dB loss of cochlear sensitivity in vivo, without disruption of mechano-electrical transduction in outer hair cells. In heterozygotes, electromotility is halved and there is a twofold (about 6 dB) increase in cochlear thresholds. These results suggest that prestin is indeed the motor protein, that there is a simple and direct coupling between electromotility and cochlear amplification, and that there is no need to invoke additional active processes to explain cochlear sensitivity in the mammalian ear.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Targeted disruption of the prestin locus.
Figure 2: Morphological and immunohistochemical analysis of mutant mice.
Figure 3: In vitro analysis of OHC electromotility in mutant mice.
Figure 4: In vivo assays of cochlear sensitivity in mutant mice.

Similar content being viewed by others

References

  1. Gold, T. Hearing. II. The physical basis of the action of the cochlea. Proc. R. Soc. Lond. B 135, 492–498 (1948)

    Article  ADS  Google Scholar 

  2. Dallos, P. & Harris, D. Properties of auditory nerve responses in absence of outer hair cells. J. Neurophysiol. 41, 365–383 (1978)

    Article  CAS  Google Scholar 

  3. Brown, M. C., Nuttall, A. L. & Masta, R. I. Intracellular recordings from cochlear inner hair cells: effects of stimulation of the crossed olivocochlear efferents. Science 222, 69–72 (1983)

    Article  ADS  CAS  Google Scholar 

  4. Dallos, P. The active cochlea. J. Neurosci. 12, 4575–4585 (1992)

    Article  CAS  Google Scholar 

  5. Brownell, W. E., Bader, C. R., Bertrand, D. & de Ribaupierre, Y. Evoked mechanical responses of isolated cochlear outer hair cells. Science 227, 194–196 (1985)

    Article  ADS  CAS  Google Scholar 

  6. Kachar, B., Brownell, W. E., Altschuler, R. & Fex, J. Electrokinetic shape changes of cochlear outer hair cells. Nature 322, 365–368 (1986)

    Article  ADS  CAS  Google Scholar 

  7. Ashmore, J. F. A fast motile response in guinea-pig outer hair cells: the cellular basis of the cochlear amplifier. J. Physiol. 388, 323–347 (1987)

    Article  CAS  Google Scholar 

  8. Ashmore, J. F. Cochlear Mechanisms (eds Wilson, J. P. & Kemp, D. T.) 107–116 (Plenum, London, 1989)

    Google Scholar 

  9. Santos-Sacchi, J. Reversible inhibition of voltage-dependent outer hair cell motility and capacitance. J. Neurosci. 11, 3096–3110 (1991)

    Article  CAS  Google Scholar 

  10. Zheng, J. et al. Prestin is the motor protein of cochlear outer hair cells. Nature 405, 149–155 (2000)

    Article  ADS  CAS  Google Scholar 

  11. Belyantseva, I. A., Adler, H. J., Curi, R., Frolenkov, G. I. & Kachar, B. Expression and localization of prestin and the sugar transporter GLUT-5 during development of electromotility in cochlear outer hair cells. J. Neurosci. 20, RC116 (2000)

    Article  CAS  Google Scholar 

  12. Oliver, D. et al. Intracellular anions as the voltage sensor of prestin, the outer hair cell motor protein. Science 292, 2340–2343 (2001)

    Article  CAS  Google Scholar 

  13. Forge, A. Structural features of the lateral walls in mammalian cochlear outer hair cells. Cell Tissue Res. 265, 473–483 (1991)

    Article  CAS  Google Scholar 

  14. Dallos, P. & Fakler, B. Prestin, a new type of motor protein. Nature Rev. Mol. Cell Biol. 3, 104–111 (2002)

    Article  CAS  Google Scholar 

  15. Bohne, B. A. & Rabbitt, K. D. Holes in the reticular lamina after noise exposure: implication for continuing damage in the organ of Corti. Hear. Res. 11, 41–53 (1983)

    Article  CAS  Google Scholar 

  16. Holt, J. R. et al. A chemical-genetic strategy implicates myosin-1c in adaptation by hair cells. Cell 108, 371–381 (2002)

    Article  CAS  Google Scholar 

  17. Kros, C. J. et al. Reduced climbing and increased slipping adaptation in cochlear hair cells of mice with Myo7a mutations. Nature Neurosci. 5, 41–47 (2002)

    Article  CAS  Google Scholar 

  18. Dallos, P. & Wang, C. Y. Bioelectric correlates of kanamycin intoxication. Audiology 13, 277–289 (1974)

    Article  CAS  Google Scholar 

  19. Kemp, D. T. Stimulated acoustic emissions from within the human auditory system. J. Acoust. Soc. Am. 64, 1386–1391 (1978)

    Article  ADS  CAS  Google Scholar 

  20. Johnstone, B. M., Patuzzi, R. & Yates, G. K. Basilar membrane measurements and the travelling wave. Hear. Res. 22, 147–153 (1986)

    Article  CAS  Google Scholar 

  21. Ruggero, M. A. & Rich, N. C. Application of a commercially-manufactured Doppler-shift laser velocimeter to the measurement of basilar-membrane vibration. Hear. Res. 51, 215–230 (1991)

    Article  CAS  Google Scholar 

  22. Sellick, P. M., Patuzzi, R. & Johnstone, B. M. Measurement of basilar membrane motion in the guinea pig using the Mossbauer technique. J. Acoust. Soc. Am. 72, 131–141 (1982)

    Article  ADS  CAS  Google Scholar 

  23. Kiang, N. Y. & Moxon, E. C. Tails of tuning curves of auditory-nerve fibers. J. Acoust. Soc. Am. 55, 620–630 (1974)

    Article  ADS  CAS  Google Scholar 

  24. Ruggero, M. A. Responses to sound of the basilar membrane of the mammalian cochlea. Curr. Opin. Neurobiol. 2, 449–456 (1992)

    Article  CAS  Google Scholar 

  25. Manley, G. A. Cochlear mechanisms from a phylogenetic viewpoint. Proc. Natl Acad. Sci. USA 97, 11736–11743 (2000)

    Article  ADS  CAS  Google Scholar 

  26. Fettiplace, R., Ricci, A. J. & Hackney, C. M. Clues to the cochlear amplifier from the turtle ear. Trends Neurosci. 24, 169–175 (2001)

    Article  CAS  Google Scholar 

  27. Hudspeth, A. J. Mechanical amplification of stimuli by hair cells. Curr. Opin. Neurobiol. 7, 480–486 (1997)

    Article  CAS  Google Scholar 

  28. Ehret, G. The Auditory Psychobiology of the Mouse (ed. Willott, J. F.)) 169–200 (Charles Thomas, Springfield, Illinois, 1983)

    Google Scholar 

  29. He, D. Z., Evans, B. N. & Dallos, P. First appearance and development of electromotility in neonatal gerbil outer hair cells. Hear. Res. 78, 77–90 (1994)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank K. Cullen for technical assistance; T. Curran, B. Fritzsch, C. A. Shera and D. Freeman for comments on the manuscript; and B. Kachar, T. Hasson and P. Gillespie for antibodies. This work is supported in part by NIH grants to M.C.L., Z.Z.H. and J.Z., NIH Cancer Center Support CORE grant, and the American Lebanese Syrian Associated Charities (ALSAC).

Author information

Author notes

  1. M. Charles Liberman and Jiangang Gao: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Otology and Laryngology, Harvard Medical School and Eaton-Peabody Laboratory, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, 02114, USA

    M. Charles Liberman

  2. Ear Infirmary,

    M. Charles Liberman

  3. Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, Tennessee, 38105, USA

    Jiangang Gao, Xudong Wu & Jian Zuo

  4. Boys Town National Research Hospital, Omaha, Nebraska, 68131, USA

    David Z. Z. He & Shuping Jia

  5. Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee, 38163, USA

    Xudong Wu

Authors
  1. M. Charles Liberman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jiangang Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David Z. Z. He
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xudong Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shuping Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jian Zuo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jian Zuo.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liberman, M., Gao, J., He, D. et al. Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier. Nature 419, 300–304 (2002). https://doi.org/10.1038/nature01059

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature01059

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing