The antidepressant fluoxetine blocks the human small conductance calcium-activated potassium channels SK1, SK2 and SK3

Neurosci Lett. 2003 Jul 31;346(1-2):85-8. doi: 10.1016/s0304-3940(03)00574-3.


The effects of fluoxetine (Prozac) on the activity of human small-conductance calcium-activated potassium (SK) channels were investigated utilizing a functional fluorescence assay with bis-(1,3-dibutylbarbituric acid)trimethine oxonol (DiBAC(4)(3)). Fluoxetine blocked SK channels stably expressed in HEK 293 cells in a concentration-dependent manner displaying half-maximal inhibitory concentrations (IC(50)) of 9 microM for hSK1, 7 microM for hSK2 and 20 microM for hSK3. The block of hSK3 channels was confirmed by whole cell patch-clamp recordings of the recombinant cells and human TE 671 cells. Fluoxetine also inhibited [(125)I]apamin binding in a concentration-dependent manner displaying IC(50) values of 63 microM for hSK1, 148 microM for hSK2 and 295 microM for hSK3. These results provide new information concerning the mechanism of therapeutic and/or side effects of one of the most widely used antidepressant drugs.

MeSH terms

  • Antidepressive Agents, Second-Generation / pharmacology*
  • Cell Line
  • Dose-Response Relationship, Drug
  • Fluoxetine / pharmacology*
  • Humans
  • Potassium Channel Blockers / pharmacology*
  • Potassium Channels / physiology*
  • Potassium Channels, Calcium-Activated / antagonists & inhibitors
  • Potassium Channels, Calcium-Activated / physiology
  • Small-Conductance Calcium-Activated Potassium Channels


  • Antidepressive Agents, Second-Generation
  • KCNN1 protein, human
  • KCNN2 protein, human
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Calcium-Activated
  • Small-Conductance Calcium-Activated Potassium Channels
  • Fluoxetine