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Science 22 June 2001:
Vol. 292. no. 5525, pp. 2340 - 2343
DOI: 10.1126/science.1060939
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Reports

Intracellular Anions as the Voltage Sensor of Prestin, the Outer Hair Cell Motor Protein

Dominik Oliver,1 David Z. Z. He,2 Nikolaj Klöcker,1 Jost Ludwig,1 Uwe Schulte,1 Siegfried Waldegger,3 J. P. Ruppersberg,1 Peter Dallos,4 Bernd Fakler1*

Outer hair cells (OHCs) of the mammalian cochlea actively change their cell length in response to changes in membrane potential. This electromotility, thought to be the basis of cochlear amplification, is mediated by a voltage-sensitive motor molecule recently identified as the membrane protein prestin. Here, we show that voltage sensitivity is conferred to prestin by the intracellular anions chloride and bicarbonate. Removal of these anions abolished fast voltage-dependent motility, as well as the characteristic nonlinear charge movement ("gating currents") driving the underlying structural rearrangements of the protein. The results support a model in which anions act as extrinsic voltage sensors, which bind to the prestin molecule and thus trigger the conformational changes required for motility of OHCs.

1 Department of Physiology II, University of Tübingen, 72074 Tübingen, Germany.
2 Boys Town National Research Hospital, Omaha, NE 68131, USA.
3 Centre of Pediatrics, University of Marburg, 35037 Marburg, Germany.
4 Auditory Physiology Laboratory, Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA.
*   To whom correspondence should be addressed. E-mail: bernd.fakler{at}uni-tuebingen.de

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