Fluoxetine inhibits A-type potassium currents in primary cultured rat hippocampal neurons

Brain Res. 2004 Aug 27;1018(2):201-7. doi: 10.1016/j.brainres.2004.05.065.


The effects of fluoxetine (Prozac) on the transient A-currents (IA) in primary cultured hippocampal neurons were examined using the whole-cell patch clamp technique. Fluoxetine did not significantly decrease the peak amplitude of whole-cell K+ currents, but it accelerated the decay rate of inactivation, and thus decreased the current amplitude at the end of the pulse. For further analysis, IA and delayed rectifier K+ currents (IDR) were isolated from total K+ currents. Fluoxetine decreased IA (the integral of the outward current) in a concentration-dependent manner with an IC50 of 5.54 microM. Norfluoxetine, the major active metabolite of fluoxetine, was a more potent inhibitor of IA than was fluoxetine, with an IC50 of 0.90 microM. Fluoxetine (3 microM) inhibited IA in a voltage-dependent manner over the whole range of membrane potentials tested. Analysis of the time dependence of inhibition gave estimates of 34.72 microM(-1) s(-1) and 116.39 s(-1) for the rate constants of association and dissociation, respectively. The resulting apparent Kd was 3.35 microM, similar to the IC50 value obtained from the concentration-response curve. In current clamp configuration, fluoxetine (3 microM) induced depolarization of resting membrane potential and reduced the rate of action potential. Our results indicate that fluoxetine produces a concentration- and voltage-dependent inhibition of IA, and that this effect could affect the excitability of hippocampal neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Fluoxetine / pharmacology*
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Hippocampus / physiology
  • Inhibitory Concentration 50
  • Membrane Potentials / drug effects
  • Neurons / drug effects*
  • Neurons / physiology
  • Patch-Clamp Techniques
  • Potassium Channels, Voltage-Gated / drug effects*
  • Rats
  • Rats, Wistar
  • Selective Serotonin Reuptake Inhibitors / pharmacology


  • Potassium Channels, Voltage-Gated
  • Serotonin Uptake Inhibitors
  • Fluoxetine