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Biophys. J. BioFAST: First Published December 13, 2004. doi:10.1529/biophysj.104.053579
© 2004 by the Biophysical Society.

A more recent version of this article appeared on March 1, 2005.
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ELECTROPHYSIOLOGY

On membrane motor activity and chloride flux in the outer hair cell: lessons learned from the environmental toxin tributyltin

Lei Song 1, Achim Seeger 1 and Joseph Santos-Sacchi 2*

1 Yale University School of Medicine
2 Yale University Sch. of Med.

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

Submitted on September 27, 2004
Revised on November 3, 2004
Accepted on 29 November 2004


  Abstract
The outer hair cell (OHC) underlies mammalian cochlea amplification, and its lateral membrane motor, prestin, which drives the cell's mechanical activity, is modulated by intracellular chloride ions. We have previously described a native non-selective conductance (GmetL) that influences OHC motor activity via Cl flux across the lateral membrane. Here we further investigate this conductance and use the environmental toxin tributyltin (TBT) to better understand Cl - prestin interactions. Capitalizing on measures of prestin-derived nonlinear capacitance to gauge Cl flux across the lateral membrane, we show that the Cl ionophore TBT, which affects neither the motor nor GmetL directly, is capable of augmenting the native flux of Cl in OHCs. These observations were confirmed using the chloride sensitive dye, MQAE. Furthermore, the compound's potent ability, at nanomolar concentrations, to equilibrate intra- and extracellular Cl concentrations is shown to surpass the effectiveness of GmetL in promoting Cl flux, and secure a quantitative analysis of Cl - prestin interactions in intact OHCs. Using malate as an anion replacement, we quantify chloride effects on the nonlinear charge density and operating voltage range of prestin. Our data additionally suggest that ototoxic effects of organotins can derive from their disruption of OHC Cl homeostasis, ultimately interfering with anionic modulation of the mammalian cochlear amplifier. Notably, this observation identifies a new environmental threat for marine mammals by TBT which is known to accumulate in the food chain.

Key Words: chloride, membrane capacitance, outer hair cell, prestin, tributyltin




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Copyright © 2004 by the Biophysical Society.