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

Eur J Pharmacol. 2002 Oct 25;453(2-3):159-66. doi: 10.1016/s0014-2999(02)02421-4.

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 microM. 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 (delta 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cochlea / cytology
  • Cochlea / drug effects*
  • Dose-Response Relationship, Drug
  • Fluoxetine / pharmacology*
  • Guinea Pigs
  • Hair Cells, Auditory, Outer / drug effects*
  • Hair Cells, Auditory, Outer / physiology
  • In Vitro Techniques
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / drug effects*
  • Serotonin Uptake Inhibitors / pharmacology*
  • Time Factors

Substances

  • Potassium Channel Blockers
  • Potassium Channels
  • Serotonin Uptake Inhibitors
  • Fluoxetine