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

G Terstappen; A Pellacani; L Aldegheri; F Graziani; C Carignani; Giordano Pula; C Virginio

doi:10.1016/S0304-3940(03)00574-3

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

G Terstappen, A Pellacani, L Aldegheri, F Graziani, C Carignani, Giordano Pula, C Virginio

Department of Life Sciences

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46 Citations (SciVal)

Abstract

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 (DiBAC4(3)). Fluoxetine blocked SK channels stably expressed in HEK 293 cells in a concentration-dependent manner displaying half-maximal inhibitory concentrations (IC50) 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 IC50 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.

Original language	English
Pages (from-to)	85-88
Number of pages	4
Journal	Neuroscience Letters
Volume	346
Issue number	1-2
DOIs	https://doi.org/10.1016/S0304-3940(03)00574-3
Publication status	Published - 31 Jul 2003

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

abstract = "The effects of fluoxetine (Prozac{\texttrademark}) 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 (DiBAC4(3)). Fluoxetine blocked SK channels stably expressed in HEK 293 cells in a concentration-dependent manner displaying half-maximal inhibitory concentrations (IC50) 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 IC50 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.",

author = "G Terstappen and A Pellacani and L Aldegheri and F Graziani and C Carignani and Giordano Pula and C Virginio",

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T1 - The antidepressant fluoxetine blocks the human small conductance calcium-activated potassium channels SK1, SK2 and SK3

AU - Terstappen, G

AU - Pellacani, A

AU - Aldegheri, L

AU - Graziani, F

AU - Carignani, C

AU - Pula, Giordano

AU - Virginio, C

PY - 2003/7/31

Y1 - 2003/7/31

N2 - 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 (DiBAC4(3)). Fluoxetine blocked SK channels stably expressed in HEK 293 cells in a concentration-dependent manner displaying half-maximal inhibitory concentrations (IC50) 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 IC50 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.

AB - 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 (DiBAC4(3)). Fluoxetine blocked SK channels stably expressed in HEK 293 cells in a concentration-dependent manner displaying half-maximal inhibitory concentrations (IC50) 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 IC50 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.

UR - http://dx.doi.org/10.1016/S0304-3940(03)00574-3

U2 - 10.1016/S0304-3940(03)00574-3

DO - 10.1016/S0304-3940(03)00574-3

M3 - Article

SN - 0304-3940

VL - 346

SP - 85

EP - 88

JO - Neuroscience Letters

JF - Neuroscience Letters

IS - 1-2

ER -

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

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