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Ca2+ current–driven nonlinear amplification by the mammalian cochlea in vitro

Abstract

An active process in the inner ear expends energy to enhance the sensitivity and frequency selectivity of hearing. Two mechanisms have been proposed to underlie this process in the mammalian cochlea: receptor potential–based electromotility and Ca2+-driven active hair-bundle motility. To link the phenomenology of the cochlear amplifier with these cellular mechanisms, we developed an in vitro cochlear preparation from Meriones unguiculatus that affords optical access to the sensory epithelium while mimicking its in vivo environment. Acoustic and electrical stimulation elicited microphonic potentials and electrically evoked hair-bundle movement, demonstrating intact forward and reverse mechanotransduction. The mechanical responses of hair bundles from inner hair cells revealed a characteristic resonance and a compressive nonlinearity diagnostic of the active process. Blocking transduction with amiloride abolished nonlinear amplification, whereas eliminating all but the Ca2+ component of the transduction current did not. These results suggest that the Ca2+ current drives the cochlear active process, and they support the hypothesis that active hair-bundle motility underlies cochlear amplification.

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Figure 1: In vitro cochlear preparation.
Figure 2: Basilar-membrane resonance.
Figure 3: Microphonic potential.
Figure 4: Electrically evoked hair-bundle movement.
Figure 5: Compressive nonlinearity and amplification.

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Acknowledgements

The authors thank A. Hinterwirth for construction of the experimental chamber, B. Fabella for computer programming, and the members of our research group for comments on the manuscript. This work was supported by US National Institutes of Health grants DC00241 and GM07739. A.J.H. is an Investigator of Howard Hughes Medical Institute.

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Correspondence to A J Hudspeth.

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Chan, D., Hudspeth, A. Ca2+ current–driven nonlinear amplification by the mammalian cochlea in vitro. Nat Neurosci 8, 149–155 (2005). https://doi.org/10.1038/nn1385

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