Te-Yu Hung1, Huai-Ying Ingrid Huang2, Sheng-Nan Wu3,4,5, Chin-Wei Huang6. 1. Department of Pediatrics, Chi-Mei Medical Center, Tainan, Taiwan. 2. Neuroscience Program, McGill University, Montréal, Quebec, Canada. 3. Department of Physiology, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan City, 70101, Taiwan. snwu@mail.ncku.edu.tw. 4. Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan City, Taiwan. snwu@mail.ncku.edu.tw. 5. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung City, Taiwan. snwu@mail.ncku.edu.tw. 6. Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan City, 70101, Taiwan. huangcw@mail.ncku.edu.tw.
Abstract
BACKGROUND: Vigabatrin (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. 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, 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. CONCLUSIONS: The 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.
BACKGROUND: Vigabatrin (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. 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, 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. CONCLUSIONS: The 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.
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