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

Biophys J. 2005 Mar;88(3):2350-62. doi: 10.1529/biophysj.104.053579. Epub 2004 Dec 13.


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 nonselective conductance (G(metL)) 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 G(metL) 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 G(metL) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Membrane / drug effects
  • Cell Membrane / physiology*
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Cells, Cultured
  • Chlorine / metabolism*
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • Hair Cells, Auditory, Outer / cytology*
  • Hair Cells, Auditory, Outer / drug effects
  • Hair Cells, Auditory, Outer / physiology*
  • Hazardous Substances / pharmacology
  • Molecular Motor Proteins / drug effects
  • Molecular Motor Proteins / physiology*
  • Trialkyltin Compounds / pharmacology*


  • Hazardous Substances
  • Molecular Motor Proteins
  • Trialkyltin Compounds
  • Chlorine
  • tributyltin