抗抑郁药氟西汀可阻断人类小电导钙激活钾通道SK1、SK2和SK3。
The antidepressant fluoxetine blocks the human small conductance calcium-activated potassium channels SK1, SK2 and SK3.
作者信息
Terstappen Georg C, Pellacani Annalisa, Aldegheri Laura, Graziani Francesca, Carignani Corrado, Pula Giordano, Virginio Caterina
机构信息
GlaxoSmithKline, Medicines Research Centre, Via A Fleming 4, 37135 Verona, Italy.
出版信息
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.
利用双（1,3 - 二丁基巴比妥酸）三甲川草酚菁（DiBAC(4)(3)）的功能性荧光测定法，研究了氟西汀（百忧解）对人小电导钙激活钾（SK）通道活性的影响。氟西汀以浓度依赖性方式稳定阻断在HEK 293细胞中稳定表达的SK通道，对hSK1的半数最大抑制浓度（IC(50)）为9 microM，对hSK2为7 microM，对hSK3为20 microM。通过重组细胞和人TE 671细胞的全细胞膜片钳记录证实了hSK3通道的阻断。氟西汀还以浓度依赖性方式抑制[(125)I]蜂毒明肽结合，对hSK1的IC(50)值为63 microM，对hSK2为148 microM，对hSK3为295 microM。这些结果为最广泛使用的抗抑郁药物之一的治疗和/或副作用机制提供了新信息。
Zotero 插件