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Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier M.Charles Liberman*, Jiangang Gao‡, David Z.Z.He§, Xudong Wu‡†, Shuping Jia§ & Jian Zuo‡ Nature 419, 300-304, 19 Sep 2002 * Department of Otology and Laryngology, Harvard Medical School and Eaton-Peabody
Laboratory, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
02114, USA 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 cells. 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 vitro.
This electromotility is thought to arise through voltage-gated conformational
changes in a membrane protein, and prestin has been proposed as this molecular
motor. 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. Comment: This report concludes a hunt of more than 20 years for the motor that amplifies sound vibrations in the inner ear of mammals. It marks a major success in hearing research, and it also highlights the powerful tools that modern gene technique now provides. A targeted gene deletion could prove that prestin is a motor protein that performs voltage-driven conformational changes in the lateral membrane of the outer hair cells in the mammalian cochlea and thus causes cellular vibrations at audio frequencies. It should be added, however, that the authors' concluding sentence of the report and the last words of the abstract "that there is no need to invoke additional active processes to explain cochlear sensitivity in the mammalian ear" are not borne out by the reported experiments. The present results prove that prestin is a necessary, but not that it is a sufficient motor for the ear's low-level amplifier. Non-mammalian vertebrates have an inner-ear amplifier that is driven by motor proteins in the hair bundles of their sensory cells. There are good reasons to assume that this motor mechanism is also conserved in mammalian hair cells. The present study shows that a hair-bundle motor would probably not add to the force of the cell body vibrations that are effected by the prestin motors. But it could lower the threshold at which they are triggered. A hair-bundle motor would mechanically amplify minute mechanical bundle responses upon extremely weak sound input and thereby increase the receptor potential that triggers the prestin motors. Perhaps further gene deletion studies can ultimately clarify this issue. (Comment Martin Braun) |