Control of mammalian cochlear amplification by chloride anions

Joseph Santos-Sacchi, Lei Song, Jiefu Zheng, Alfred Nuttall

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Chloride ions have been hypothesized to interact with the membrane outer hair cell (OHC) motor protein, prestin on its intracellular domain to confer voltage sensitivity (Oliver et al., 2001). Thus, we hypothesized previously that transmembrane chloride movements via the lateral membrane conductance of the cell, GmetL, could serve to underlie cochlear amplification in the mammal. Here, we report on experimental manipulations of chloride-dependent OHC motor activity in vitro and in vivo. In vitro, we focused on the signature electrical characteristic of the motor, the nonlinear capacitance of the cell. Using the well known ototoxicant, salicylate, which competes with the putative anion binding or interaction site of prestin to assess level-dependent interactions of chloride with prestin, we determined that the resting level of chloride in OHCs is near or below 10 mM, whereas perilymphatic levels are known to be ∼140 mM. With this observation, we sought to determine the effects of perilymphatic chloride level manipulations of basilar membrane amplification in the living guinea pig. By either direct basolateral perfusion of the OHC with altered chloride content perilymphatic solutions or by the use of tributyltin, a chloride ionophore, we found alterations in OHC electromechanical activity and cochlear amplification, which are fully reversible. Because these anionic manipulations do not impact on the cation selective stereociliary process or the endolymphatic potential, our data lend additional support to the argument that prestin activity dominates the process of mammalian cochlear amplification.

Original languageEnglish (US)
Pages (from-to)3992-3998
Number of pages7
JournalJournal of Neuroscience
Volume26
Issue number15
DOIs
StatePublished - 2006

Fingerprint

Outer Auditory Hair Cells
Cochlea
Anions
Chlorides
Basilar Membrane
Salicylates
Ionophores
Cations
Mammals
Guinea Pigs
Motor Activity
Perfusion
Cell Membrane
Ions
Membranes
Proteins

Keywords

  • Basilar membrane
  • Capacitance
  • Chloride
  • Cochlea
  • Hearing
  • Outer hair cell

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Control of mammalian cochlear amplification by chloride anions. / Santos-Sacchi, Joseph; Song, Lei; Zheng, Jiefu; Nuttall, Alfred.

In: Journal of Neuroscience, Vol. 26, No. 15, 2006, p. 3992-3998.

Research output: Contribution to journalArticle

Santos-Sacchi, Joseph ; Song, Lei ; Zheng, Jiefu ; Nuttall, Alfred. / Control of mammalian cochlear amplification by chloride anions. In: Journal of Neuroscience. 2006 ; Vol. 26, No. 15. pp. 3992-3998.
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