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Full-Text Articles in Laboratory and Basic Science Research
Inhibition Of Astroglial Kir4.1 Channels By Selective Serotonin Reuptake Inhibitors, Y. Ohno, H. Hibino, Christoph Lossin, A. Inanobe, Y. Kurachi
Inhibition Of Astroglial Kir4.1 Channels By Selective Serotonin Reuptake Inhibitors, Y. Ohno, H. Hibino, Christoph Lossin, A. Inanobe, Y. Kurachi
Christoph Lossin, Ph.D.
The inwardly rectifying K+ (Kir) channel Kir4.1 is responsible for astroglial K+ buffering. We recently found that tricyclic antidepressants (TCAs) inhibit Kir4.1 channel currents, which suggests that astroglial Kir currents might be involved in the pharmacological action of antidepressants. We therefore further examined the effects of the currently most popular antidepressants, selective serotonin reuptake inhibitors (SSRIs), and other related agents on Kir4.1 channels heterologously expressed in HEK293T cells. The whole-cell patch clamp technique was used. Fluoxetine, the typical SSRI, inhibited Kir4.1 channel currents in a concentration-dependent manner with an IC50 value of 15.2 microM. The inhibitory effect of fluoxetine was …
Inhibition Of Astroglial Inwardly Rectifying Kir4.1 Channels By A Tricyclic Antidepressant, Nortriptyline., S. Su, Y. Ohno, Christoph Lossin, A. Inanobe, Y. Kurachi
Inhibition Of Astroglial Inwardly Rectifying Kir4.1 Channels By A Tricyclic Antidepressant, Nortriptyline., S. Su, Y. Ohno, Christoph Lossin, A. Inanobe, Y. Kurachi
Christoph Lossin, Ph.D.
The inwardly rectifying K(+) (Kir) channel Kir4.1 is responsible for astroglial K(+) buffering. We examined the effects of nortriptyline, a tricyclic antidepressant (TCA), on Kir4.1 channel currents heterologously expressed in HEK293T cells, using a whole-cell patch-clamp technique. Nortriptyline (3-300 microM) reversibly inhibited Kir4.1 currents in a concentration-dependent manner, whereas it marginally affected neuronal Kir2.1 currents. The inhibition of Kir4.1 channels by nortriptyline depended on the voltage difference from the K(+) equilibrium potential (E(K)), with greater potency at more positive potentials. Blocking kinetics of the drug could be described by first-order kinetics, where dissociation of the drug slowed down and association …