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

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.

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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.

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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).

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Correspondence to Jian Zuo.

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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

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