Actions of epoxyeicosatrienoic acid on large-conductance Ca2+-activated K+ channels in pituitary GH3 cells

Sheng-Nan Wu, Hui Fang Li, Hung Ting Chiang

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Epoxyeicosatrienoic acids (EETs), a family of cytochrome P450 epoxygenase metabolites of arachidonic acid, are believed to have an autocrine or paracrine role in the regulation of neurons or neuroendocrine cells. The effects of 14,15-EET on ionic currents were investigated in rat pituitary GH3 cells. In the whole-cell configuration, 14,15-EET (3 μM) reversibly increased the amplitude of the Ca2+-activated K+ current (I(K(Ca))). The 14,15-EET-induced increase in I(K(Ca)) was unaffected in the presence of 10 μM thyrotropin-releasing hormone externally or 10 μM inositol trisphosphate in the recording pipette. In cells preincubated with pertussis toxin or herbimycin A, the 14,15-EET-induced increase in I(K(Ca)) was also not changed. In the inside-out configuration, 14,15-EET applied intracellularly did not change single-channel conductance, but did increase the opening probability of large-conductance Ca2+-activated K+ (BK(Ca)) channels. 14,15-EET (3 μM) shifted the activation curve of BK(Ca) channels to less positive membrane potential by approximately 15 mV. The change in the kinetic behavior of BK(Ca) channels caused by 14,15-EET is explained by a lengthening of open and a shortening of closed times. 14,15-EET increased the activity of BK(Ca) channels in a concentration-dependent manner with an EC50 value of 1 μM. However, 14,15-EET did not affect the Ca2+ sensitivity of BK(Ca) channels. The present study indicates that 14,15-EET is an opener of BK(Ca) channels in GH3 cells and that the stimulatory effect of 14,15-EET on these channels may, at least in part, contribute to the underlying cellular mechanisms by which EETs affect neuronal or neuroendocrine function. Copyright (C) 2000 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)251-262
Number of pages12
JournalBiochemical Pharmacology
Volume60
Issue number2
DOIs
Publication statusPublished - 2000 Jul 15

Fingerprint

Calcium-Activated Potassium Channels
Large-Conductance Calcium-Activated Potassium Channels
Acids
14,15-epoxy-5,8,11-eicosatrienoic acid
Neuroendocrine Cells
Thyrotropin-Releasing Hormone
Pertussis Toxin
Inositol
Metabolites
Arachidonic Acid
Membrane Potentials
Cytochrome P-450 Enzyme System
Neurons
Rats
Chemical activation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

Cite this

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title = "Actions of epoxyeicosatrienoic acid on large-conductance Ca2+-activated K+ channels in pituitary GH3 cells",
abstract = "Epoxyeicosatrienoic acids (EETs), a family of cytochrome P450 epoxygenase metabolites of arachidonic acid, are believed to have an autocrine or paracrine role in the regulation of neurons or neuroendocrine cells. The effects of 14,15-EET on ionic currents were investigated in rat pituitary GH3 cells. In the whole-cell configuration, 14,15-EET (3 μM) reversibly increased the amplitude of the Ca2+-activated K+ current (I(K(Ca))). The 14,15-EET-induced increase in I(K(Ca)) was unaffected in the presence of 10 μM thyrotropin-releasing hormone externally or 10 μM inositol trisphosphate in the recording pipette. In cells preincubated with pertussis toxin or herbimycin A, the 14,15-EET-induced increase in I(K(Ca)) was also not changed. In the inside-out configuration, 14,15-EET applied intracellularly did not change single-channel conductance, but did increase the opening probability of large-conductance Ca2+-activated K+ (BK(Ca)) channels. 14,15-EET (3 μM) shifted the activation curve of BK(Ca) channels to less positive membrane potential by approximately 15 mV. The change in the kinetic behavior of BK(Ca) channels caused by 14,15-EET is explained by a lengthening of open and a shortening of closed times. 14,15-EET increased the activity of BK(Ca) channels in a concentration-dependent manner with an EC50 value of 1 μM. However, 14,15-EET did not affect the Ca2+ sensitivity of BK(Ca) channels. The present study indicates that 14,15-EET is an opener of BK(Ca) channels in GH3 cells and that the stimulatory effect of 14,15-EET on these channels may, at least in part, contribute to the underlying cellular mechanisms by which EETs affect neuronal or neuroendocrine function. Copyright (C) 2000 Elsevier Science Inc.",
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Actions of epoxyeicosatrienoic acid on large-conductance Ca2+-activated K+ channels in pituitary GH3 cells. / Wu, Sheng-Nan; Li, Hui Fang; Chiang, Hung Ting.

In: Biochemical Pharmacology, Vol. 60, No. 2, 15.07.2000, p. 251-262.

Research output: Contribution to journalArticle

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N2 - Epoxyeicosatrienoic acids (EETs), a family of cytochrome P450 epoxygenase metabolites of arachidonic acid, are believed to have an autocrine or paracrine role in the regulation of neurons or neuroendocrine cells. The effects of 14,15-EET on ionic currents were investigated in rat pituitary GH3 cells. In the whole-cell configuration, 14,15-EET (3 μM) reversibly increased the amplitude of the Ca2+-activated K+ current (I(K(Ca))). The 14,15-EET-induced increase in I(K(Ca)) was unaffected in the presence of 10 μM thyrotropin-releasing hormone externally or 10 μM inositol trisphosphate in the recording pipette. In cells preincubated with pertussis toxin or herbimycin A, the 14,15-EET-induced increase in I(K(Ca)) was also not changed. In the inside-out configuration, 14,15-EET applied intracellularly did not change single-channel conductance, but did increase the opening probability of large-conductance Ca2+-activated K+ (BK(Ca)) channels. 14,15-EET (3 μM) shifted the activation curve of BK(Ca) channels to less positive membrane potential by approximately 15 mV. The change in the kinetic behavior of BK(Ca) channels caused by 14,15-EET is explained by a lengthening of open and a shortening of closed times. 14,15-EET increased the activity of BK(Ca) channels in a concentration-dependent manner with an EC50 value of 1 μM. However, 14,15-EET did not affect the Ca2+ sensitivity of BK(Ca) channels. The present study indicates that 14,15-EET is an opener of BK(Ca) channels in GH3 cells and that the stimulatory effect of 14,15-EET on these channels may, at least in part, contribute to the underlying cellular mechanisms by which EETs affect neuronal or neuroendocrine function. Copyright (C) 2000 Elsevier Science Inc.

AB - Epoxyeicosatrienoic acids (EETs), a family of cytochrome P450 epoxygenase metabolites of arachidonic acid, are believed to have an autocrine or paracrine role in the regulation of neurons or neuroendocrine cells. The effects of 14,15-EET on ionic currents were investigated in rat pituitary GH3 cells. In the whole-cell configuration, 14,15-EET (3 μM) reversibly increased the amplitude of the Ca2+-activated K+ current (I(K(Ca))). The 14,15-EET-induced increase in I(K(Ca)) was unaffected in the presence of 10 μM thyrotropin-releasing hormone externally or 10 μM inositol trisphosphate in the recording pipette. In cells preincubated with pertussis toxin or herbimycin A, the 14,15-EET-induced increase in I(K(Ca)) was also not changed. In the inside-out configuration, 14,15-EET applied intracellularly did not change single-channel conductance, but did increase the opening probability of large-conductance Ca2+-activated K+ (BK(Ca)) channels. 14,15-EET (3 μM) shifted the activation curve of BK(Ca) channels to less positive membrane potential by approximately 15 mV. The change in the kinetic behavior of BK(Ca) channels caused by 14,15-EET is explained by a lengthening of open and a shortening of closed times. 14,15-EET increased the activity of BK(Ca) channels in a concentration-dependent manner with an EC50 value of 1 μM. However, 14,15-EET did not affect the Ca2+ sensitivity of BK(Ca) channels. The present study indicates that 14,15-EET is an opener of BK(Ca) channels in GH3 cells and that the stimulatory effect of 14,15-EET on these channels may, at least in part, contribute to the underlying cellular mechanisms by which EETs affect neuronal or neuroendocrine function. Copyright (C) 2000 Elsevier Science Inc.

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