Depressive Effectiveness of Vigabatrin (y-Vinyl-GABA), an Antiepileptic Drug, in Intermediate-conductance Calcium-Activated Potassium Channels in Human Glioma Cells

Abstract

Background: Vigabatrin (VGB, y-vinyl-GABA) is an approved non-traditional antiepileptic drug that has been revealed to have the therapeutic propensity for brain tumors; however, its ionic effects in glioma cells remain unclear to a large extent.Methods: With the aid of patch-clamp technology, we investigated the effects of VGB on various ionic currents in the glioblastoma multiforme cell line 13-06-MG.Results: In cell-attached configuration, addition of VGB concentration-dependently lessened the activity of intermediate-conductance Ca 2+ -activated K + (IK Ca ) channels, while subsequent application of DCEBIO (5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one) thwarted the VGB-induced inhibition of IK Ca channels. Neither the activity of large-conductance Ca 2+ -activated (BK Ca ) nor that of inwardly rectifying K + (K IR ) channels was adjusted by the presence of VGB in human 13-06-MG cells. However, in the continued presence of VGB, the addition of GAL-021 or BaCl 2 effectively suppressed BK Ca and K IR channels.Conclusion: The inhibitory effect of VGB on IK Ca channels demonstrated in the current study could be an unidentified but important underlying mechanism of VGB-induced antineoplastic ( e.g. , anti-glioma) actions.