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First published online on January 31, 2003.
 Copyright © 2003 by The Physiological Society
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Received November 22, 2002
Accepted after revision December 18, 2002

Cl- flux through a non-selective, stretch-sensitive conductance influences the outer hair cell motor of the guinea-pig

Volodymyr Rybalchenko1 and J. Santos-Sacchi2*

1 Departments of Surgery (Otolaryngology) and Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510 USA
2 Department of Surgery (Otolaryngology), BML 244, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA

* To whom correspondence should be addressed. E-mail: joseph.santos-sacchi{at}yale.edu.

Outer hair cells underlie high frequency cochlear amplification in mammals. Fast somatic motility can be driven by voltage-dependent conformational changes in the motor protein, prestin, which resides exclusively within lateral plasma membrane of the cell. Yet, how a voltage-driven motor could contribute to high frequency amplification, despite the low-pass membrane filter of the cell, remains an enigma. The recent identification of prestin's Cl- sensitivity revealed an alternative mechanism in which intracellular Cl- fluctuations near prestin could influence the motor. We report the existence of a stretch-sensitive conductance within the lateral membrane that passes anions and cations and is gated at acoustic rates. The resultant intracellular Cl- oscillations near prestin may drive motor protein transitions, as evidenced by pronounced shifts in prestin's state-probability function along the voltage axis. The sensitivity of prestin's state probability to intracellular Cl- levels betokens a more complicated role for Cl- than a simple extrinsic voltage sensor. Instead, we suggest an allosteric modulation of prestin by Cl- and other anions. Finally, we hypothesize that prestin sensitivity to anion flux through the mechanically activated lateral membrane can provide a driving force that circumvents the membrane's low-pass filter, thus permitting amplification at high acoustic frequencies.




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