TY - JOUR
T1 - Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier
AU - Liberman, M. Charles
AU - Gao, Jiangang
AU - He, David Z.Z.
AU - Wu, Xudong
AU - Jia, Shuping
AU - Zuo, Jian
N1 - Funding Information:
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).
Funding Information:
We thank G. Feng for providing the YFP-G mice. L.C.K. is an Investigator in the Howard Hughes Medical Institute, L.B. is a Burroughs Wellcome Fellow in Neuroscience, and grant support to P.M. was from the NIH.
PY - 2002/9/19
Y1 - 2002/9/19
N2 - 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 cells1-4. 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 vitro5-7. This electromotility is thought to arise through voltage-gated conformational changes in a membrane protein8,9, and prestin has been proposed as this molecular motor10-12. 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.
AB - 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 cells1-4. 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 vitro5-7. This electromotility is thought to arise through voltage-gated conformational changes in a membrane protein8,9, and prestin has been proposed as this molecular motor10-12. 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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U2 - 10.1038/nature01059
DO - 10.1038/nature01059
M3 - Article
C2 - 12239568
AN - SCOPUS:0037136582
VL - 419
SP - 300
EP - 304
JO - Nature
JF - Nature
SN - 0028-0836
IS - 6904
ER -