Depressive effectiveness of vigabatrin (γ-vinyl-GABA), an antiepileptic drug, in intermediate-conductance calcium-activated potassium channels in human glioma cells

  • BMC Pharmacol Toxicol. 2021 Jan 13;22(1):6. doi: 10.1186/s40360-021-00472-3.
Te-Yu Hung  1 ,  Huai-Ying Ingrid Huang  2 ,  Sheng-Nan Wu  3  4  5 ,  Chin-Wei Huang  6
Affiliations
  • 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. [email protected].
  • 4. Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan City, Taiwan. [email protected].
  • 5. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung City, Taiwan. [email protected].
  • 6. Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan City, 70101, Taiwan. [email protected].
PMID: 33441172 DOI: 10.1186/s40360-021-00472-3
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.

Keywords
Glioma cell; Intermediate-conductance Ca2+-activated K+ channel; Vigabatrin.
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