Stimulatory effects of δ-hexachlorocyclohexane on Ca2+-activated K+ currents in GH3 lactotrophs

Sheng Nan Wu, Hui Fang Li, Hung Ting Chiang

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19 Citations (Scopus)

Abstract

δ-Hexachlorocyclohexane (δ-HCH), a lipophilic neurodepressant agent, has been shown to inhibit neurotransmitter release and stimulate ryanodine- sensitive Ca2+ channels. However, the effect of δ-HCH on neuronal activity remains unclear, although it may enhance the γ-aminobutyric acid-induced current. Its effects on ionic currents were investigated in rat pituitary GH3 cells and human neuroblastoma IMR-32 cells. In GH3 cells, δ-HCH increased the amplitude of Ca2+-activated K+ current (I(K(Ca))). δ-HCH (100 μM) slightly inhibited the amplitude of voltage-dependent K+ current. δ-HCH (30 μM) suppressed voltage-dependent L-type Ca2+ current (I(Ca, L)), whereas γ-HCH (30 μM) had no effect on I(Ca, L). In the inside-out configuration, δ-HCH applied intracellularly did not change the single channel conductance of large conductance Ca2+-activated K+ (BK(Ca)) channels; however, it did increase the channel activity. The δ-HCH-mediated increase in the channel activity is mainly mediated by its increase in the number of long-lived openings. δ-HCH reversibly increased the activity of BK(Ca) channels in a concentration-dependent manner with an EC50 value of 20 μM. δ-HCH also caused a left shift in the midpoint for the voltage- dependent opening. In contrast, γ-HCH (30 μM) suppressed the activity of BK(Ca) channels. Under the current-clamp mode, δ-HCH (30 μM) reduced the firing rate of spontaneous action potentials; however, γ-HCH (30 μM) increased it. In neuroblastoma IMR-32 cells, δ-HCH also increased the amplitude of I(K(Ca)) and stimulated the activity of intermediate-conductance K(Ca) channels. This study provides evidence that δ-HCH is an opener of K(Ca) channels. The effects of δ-HCH on these channels may partially, if not entirely, be responsible for the underlying cellular mechanisms by which δ- HCH affects neuronal or neuroendocrine function.

Original languageEnglish
Pages (from-to)865-873
Number of pages9
JournalMolecular Pharmacology
Volume57
Issue number5
Publication statusPublished - 2000 May 22

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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