Abstract
BackgroundVigabatrin (VGB) is an approved non-traditional antiepileptic drug that has been revealed to have potential for treating brain tumors; however, its effect on ionic channels in glioma cells remains largely unclear.MethodsWith 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.ResultsIn cell-attached configuration, VGB concentration-dependently reduced the activity of intermediate-conductance Ca2+-activated K+ (IKCa) channels, while DCEBIO (5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one) counteracted the VGB-induced inhibition of IKCa channels. However, the activity of neither large-conductance Ca2+-activated (BKCa) nor inwardly rectifying K+ (KIR) channels were affected by the presence of VGB in human 13–06-MG cells. However, in the continued presence of VGB, the addition of GAL-021 or BaCl2 effectively suppressed BKCa and KIR channels.ConclusionsThe inhibitory effect of VGB on IKCa channels demonstrated in the current study could be an important underlying mechanism of VGB-induced antineoplastic (e.g., anti-glioma) actions.
Highlights
Vigabatrin (VGB) is an approved non-traditional antiepileptic drug that has been revealed to have potential for treating brain tumors; its effect on ionic channels in glioma cells remains largely unclear
Vigabatrin (VGB; γ-vinyl-gamma-aminobutyric acid [γvinyl-GABA]) is an approved antiepileptic drug, which is tailored as an adjuvant therapy for adults with refractory partial epilepsy; it is used for the treatment of infantile spasms [1,2,3]
VGB and the activity of IKCa channels in 13–06-MG cells Experiments to evaluate the effect of VGB on IKCa channel activity were performed
Summary
Vigabatrin (VGB) is an approved non-traditional antiepileptic drug that has been revealed to have potential for treating brain tumors; its effect on ionic channels in glioma cells remains largely unclear. IKCa channels ( known as KCa3.1, SK4, IKCa1, or KCNN4) are encoded by the KCNN4 gene These channels have been cloned from human, mouse, or rat tissues; and, their activities are viewed to be associated with various cellular functions, which include hormonal secretion, cell motility or proliferation, and the regulation of Ca2+ influx or K+ efflux. All of these underlying mechanisms have been extensively studied in different types of non-excitable or neoplastic cells [8,9,10]. The modulators of IKCa channels represent a potential therapeutic approach for a variety of diseases, at malignant gliomas [7, 13]
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