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

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 μM for hSK1, 7 μM for hSK2 and 20 μM 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 [ 125I]apamin binding in a concentration-dependent manner displaying IC 50 values of 63 μM for hSK1, 148 μM for hSK2 and 295 μM 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.