Inhibition of SK3 channels in the TE671 human medulloblastoma cell line by desipramine and imipramine.
The TE671 human medulloblastoma cell line endogenously expresses SK3 channels. Using patch clamp, we tested the effects on this current of desipramine and imipramine. In both cases, we observed a complete, reversible and concentration-dependent block. The interaction of desipramine with the selective SK3 blocker, apamin, was studied in more detail. Co-application of desipramine and apamin at concentrations close to their IC(50) produced an additive effect that was significantly higher than that of each compound alone. This effect was also observed at IC(25) concentrations. Collectively, these data provide evidence against a common site of action for desipramine and apamin.
Carignani
Corrado
C
Psychiatry CEDD, GlaxoSmithKline, Medicines Research Centre, Via Fleming, 4, 37100 Verona, Italy. cc28711@gsk.com
Corsi
Mauro
M
D003891:Desipramine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007099:Imipramine / Q000494:pharmacology*; D008527:Medulloblastoma / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism* / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D014407:Tumor Cells, Cultured
C406328:KCNN3 protein, human; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D007099:Imipramine; D003891:Desipramine