Arecoline inhibits intermediate-conductance calcium-activated potassium channels in human glioblastoma cell lines

Edmund Cheung So, Yan Ming Huang, Chung-Hsi Hsing, Yu Kai Liao, Sheng Nan Wu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Arecoline (ARE) is an alkaloid-type natural product from areca nut. This compound has numerous pharmacological and toxicological effects. Whether this agent interacts with ion channels to perturb functional activity of cells remains unknown. The effects of ARE on ionic currents were studied in glioma cell lines (U373 and U87MG) using patch-clamp technique. Like TRAM-34(1-[(2-chlorophenyl)-diphenylmethyl]pyrazole), ARE suppressed the amplitude of whole-cell voltage-gated K+ currents in U373 cells elicited by a ramp voltage clamp. In cell-attached configuration, ARE did not modify the single-channel conductance of intermediate-conductance Ca2+-activated K+ (IKCa) channels; however, it did reduce channel activity. Its inhibition of IKCa channels was accompanied by a significant lengthening in the slow component of mean closed time of IKCa channels. Based on minimal kinetic scheme, the dissociation constant (KD) required for ARE-mediated prolongation of mean closed time was 11.2 μM. ARE-induced inhibition of IKCa channels was voltage-dependent. Inability of ARE to perturb the activity of large-conductance Ca2+-activated K+ (BKCa) channels was seen. Under current-clamp recordings, ARE depolarized the membrane of U373 cells and DCEBIO reversed ARE-induced depolarization. Similarly, ARE suppressed IKCa-channel activities in oral keratinocytes. This study provides the evidence that ARE block IKCa channels in a concentration, voltage and state-dependent manner. ARE-induced block of IKCa channels is unrelated to the binding of muscarinic receptors. The effects of ARE on these channels may partially be responsible for the underlying cellular mechanisms by which it influences the functional activities of glioma cells or oral keratinocytes, if similar findings occur in vivo.

Original languageEnglish
Pages (from-to)177-187
Number of pages11
JournalEuropean Journal of Pharmacology
Volume758
DOIs
Publication statusPublished - Jul 5 2015
Externally publishedYes

Fingerprint

Intermediate-Conductance Calcium-Activated Potassium Channels
Arecoline
Glioblastoma
Cell Line
Calcium-Activated Potassium Channels
Keratinocytes
Glioma
Areca
Architectural Accessibility
Nuts

Keywords

  • Arecoline
  • Glioma cells
  • Intermediate-conductance Ca<sup>2+</sup>-activated
  • K<sup>+</sup> channel
  • K<sup>+</sup> current

ASJC Scopus subject areas

  • Pharmacology

Cite this

Arecoline inhibits intermediate-conductance calcium-activated potassium channels in human glioblastoma cell lines. / So, Edmund Cheung; Huang, Yan Ming; Hsing, Chung-Hsi; Liao, Yu Kai; Wu, Sheng Nan.

In: European Journal of Pharmacology, Vol. 758, 05.07.2015, p. 177-187.

Research output: Contribution to journalArticle

So, Edmund Cheung ; Huang, Yan Ming ; Hsing, Chung-Hsi ; Liao, Yu Kai ; Wu, Sheng Nan. / Arecoline inhibits intermediate-conductance calcium-activated potassium channels in human glioblastoma cell lines. In: European Journal of Pharmacology. 2015 ; Vol. 758. pp. 177-187.
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abstract = "Arecoline (ARE) is an alkaloid-type natural product from areca nut. This compound has numerous pharmacological and toxicological effects. Whether this agent interacts with ion channels to perturb functional activity of cells remains unknown. The effects of ARE on ionic currents were studied in glioma cell lines (U373 and U87MG) using patch-clamp technique. Like TRAM-34(1-[(2-chlorophenyl)-diphenylmethyl]pyrazole), ARE suppressed the amplitude of whole-cell voltage-gated K+ currents in U373 cells elicited by a ramp voltage clamp. In cell-attached configuration, ARE did not modify the single-channel conductance of intermediate-conductance Ca2+-activated K+ (IKCa) channels; however, it did reduce channel activity. Its inhibition of IKCa channels was accompanied by a significant lengthening in the slow component of mean closed time of IKCa channels. Based on minimal kinetic scheme, the dissociation constant (KD) required for ARE-mediated prolongation of mean closed time was 11.2 μM. ARE-induced inhibition of IKCa channels was voltage-dependent. Inability of ARE to perturb the activity of large-conductance Ca2+-activated K+ (BKCa) channels was seen. Under current-clamp recordings, ARE depolarized the membrane of U373 cells and DCEBIO reversed ARE-induced depolarization. Similarly, ARE suppressed IKCa-channel activities in oral keratinocytes. This study provides the evidence that ARE block IKCa channels in a concentration, voltage and state-dependent manner. ARE-induced block of IKCa channels is unrelated to the binding of muscarinic receptors. The effects of ARE on these channels may partially be responsible for the underlying cellular mechanisms by which it influences the functional activities of glioma cells or oral keratinocytes, if similar findings occur in vivo.",
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AU - Wu, Sheng Nan

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