Prestin-based outer hair cell electromotility in knockin mice does not appear to adjust the operating point of a cilia-based amplifier

doi:10.1073/pnas.0700356104

Prestin-based outer hair cell electromotility in knockin mice does not appear to adjust the operating point of a cilia-based amplifier

*Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105;
^†Department of Biomedical Sciences, Creighton University, Omaha, NE 68178; and
Departments of ^‡Communication Sciences and Disorders and
^§Neurobiology and Physiology, Northwestern University, Evanston, IL 60208

Edited by Charles F. Stevens, The Salk Institute for Biological Studies, La Jolla, CA, and approved May 18, 2007 (received for review January 15, 2007)

Abstract

The remarkable sensitivity and frequency selectivity of the mammalian cochlea is attributed to a unique amplification process that resides in outer hair cells (OHCs). Although the mammalian-specific somatic motility is considered a substrate of cochlear amplification, it has also been proposed that somatic motility in mammals simply acts as an operating-point adjustment for the ubiquitous stereocilia-based amplifier. To address this issue, we created a mouse model in which a mutation (C1) was introduced into the OHC motor protein prestin, based on previous results in transfected cells. In C1/C1 knockin mice, localization of C1-prestin, as well as the length and number of OHCs, were all normal. In OHCs isolated from C1/C1 mice, nonlinear capacitance and somatic motility were both shifted toward hyperpolarization, so that, compared with WT controls, the amplitude of cycle-by-cycle (alternating, or AC) somatic motility remained the same, but the unidirectional (DC) component reversed polarity near the OHC's presumed in vivo resting membrane potential. No physiological defects in cochlear sensitivity or frequency selectivity were detected in C1/C1 or C1/+ mice. Hence, our results do not support the idea that OHC somatic motility adjusts the operating point of a stereocilia-based amplifier. However, they are consistent with the notion that the AC component of OHC somatic motility plays a dominant role in mammalian cochlear amplification.

Footnotes

^¶To whom correspondence should be addressed. E-mail: jian.zuo{at}stjude.org
Author contributions: M.C., D.Z.H., P.D., and J. Zuo contributed equally to this work; J.G., M.C., D.Z.H., P.D., and J. Zuo designed research; J.G., X. Wang, X. Wu, S.A., K.H., S.J., K.M., M.P., and J. Zheng performed research; J.G., X. Wang, X. Wu, J. Zheng, M.C., D.Z.H., P.D., and J. Zuo analyzed data; and J. Zheng, M.C., D.Z.H., P.D., and J. Zuo wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
↵ ‖ Huynh, K., Edge, R., Gao, J., Zuo, J., Dallos, P., Cheatham, M. A. (2006) ARO Midwinter Meeting, no. 725.
↵ ** Huynh, K., Cheatham, M. A., Zheng, J., Dallos, P. (2006) ARO Midwinter Meeting, no. 651.
This article contains supporting information online at www.pnas.org/cgi/content/full/0700356104/DC1.
Abbreviations:

C1-prestin,

prestin with the C1 mutation (K233Q, K235Q, R236Q);

CAP,

compound action potential;

CM,

cochlear microphonic;

NLC,

nonlinear capacitance;

OHC,

outer hair cell;

Pn,

postnatal day n;

Vpkcm,

voltage at peak NLC.