Inhibition of K+ currents of outer hair cells in guinea pig cochlea by fluoxetine

Jing Tan Bian*, Jay Z. Yeh, Gary L. Aistrup, Toshio Narahashi, Ernest J. Moore

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The effects of fluoxetine (Prozac®), a widely used antidepressant drug, on K+ channel in outer hair cells isolated from guinea pig cochlea were studied using the whole-cell patch clamp technique. Fluoxetine potently inhibited leak K+ currents with an IC50 of 0.78 μM. The inhibition was reversible and voltage-independent. At 45- to 103-fold higher concentrations than the plasma levels, fluoxetine reversibly blocked voltage-activated K+ currents. Kinetics of the current in the presence of fluoxetine resembled the control current, and the inhibition was not use-dependent. Neither the activation curve nor the reversal potential was affected by fluoxetine. This inhibition was voltage-dependent with an electric distance (δ value) of the binding site of at least 26% of the membrane field from the cytoplasmic side. Use-independent inhibition suggests that fluoxetine blocks the channel before its opening or instantly blocks the open channel. This is the first study of the action of this compound on K+ channel of outer hair cells of the mammalian inner ear. We conclude that the block of the leak K+ currents can occur at therapeutic levels of fluoxetine. Since the voltage-activated K+ currents are not potently blocked by fluoxetine, this action might not be related to its antidepressant action or adverse effects.

Original languageEnglish (US)
Pages (from-to)159-166
Number of pages8
JournalEuropean Journal of Pharmacology
Volume453
Issue number2-3
DOIs
StatePublished - Oct 25 2002

Keywords

  • Antidepressant
  • Cochlea
  • Fluoxetine
  • K current
  • Outer hair cell
  • Voltage-activated

ASJC Scopus subject areas

  • Pharmacology

Fingerprint

Dive into the research topics of 'Inhibition of K<sup>+</sup> currents of outer hair cells in guinea pig cochlea by fluoxetine'. Together they form a unique fingerprint.

Cite this