抄録
The inwardly rectifying Kir4.1 channels are predominantly expressed on astrocytes in the brain, where they play a crucial role in the spatial potassium buffering. We previously reported that the tricyclic antidepressants such as nortriptyline produce a voltage-dependent inhibition of Kir4.1 channel currents. Here we extended the evaluation for various antidepressants to further characterize their actions on Kir4.1 channels, using a whole-cell patch-clamp technique. Kir channels were expressed heterogeneously in HEK293T cells and the step pulse-induced Kir currents were measured. Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), reversibly inhibited Kir4.1 currents in a concentration-dependent manner. The inhibitory effect of fluoxetine was more potent than that of nortriptyline and virtually voltage-independent. When compared with other Kir channel subtypes, fluoxetine inhibited Kir4.1/Kir5.1 channels, but barely Kir1.1 or Kir2.1 channels. Other SSRIs, sertraline and fluvoxamine, also inhibited Kir4.1 channels whereas the actions of tetracyclic (i.e., mianserin) or 5-HT1A-related (i.e., buspirone) antidepressant were negligible. The present study demonstrates for the first time that SSRIs, such as sertraline and fluoxetine, potently block astroglial K+-buffering Kir4.1 channels. These actions might be involved in therapeutic and/or adverse reactions of the antidepressants. [J Physiol Sci. 2007;57 Suppl:S231]
