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 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.
Terstappen
Georg C
GC
GlaxoSmithKline, Medicines Research Centre, Via A Fleming 4, 37135 Verona, Italy. gterstappen@sienabiotech.com
Pellacani
Annalisa
A
Aldegheri
Laura
L
Graziani
Francesca
F
Carignani
Corrado
C
Pula
Giordano
G
Virginio
Caterina
C
D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology*; D006801:Humans; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000502:physiology; D051640:Small-Conductance Calcium-Activated Potassium Channels
D018687:Antidepressive Agents, Second-Generation; C496894:KCNN1 protein, human; C496897:KCNN2 protein, human; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D005473:Fluoxetine