Regulation of Ca2+-activated K+ currents by ciglitazone in rat pituitary GH3 cells

Sheng-Nan Wu, L. L.T. Ho, H. F. Li, H. T. Chiang

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: Ciglitazone, an antidiabetic agent of the thiazolidinedione family, is known to be an activator of the peroxisome-proliferator activator receptor (PPAR)-γ. The underlying mechanism of ciglitazone actions on ionic currents in neuroendocrine ceils remains unclear. Methods: The effects of ciglitazone on ionic currents were investigated in rat pituitary GH3 cells using the whole-cell and inside-out configurations of the patch-clamp technique. Results: In GH3 cells, ciglitazone at 3-300 μmol/L caused a reversible increase in the amplitude of the Ca2+-activated K+ current (I(K(Ca))) with a half-maximal concentration of 16 μmol/L. Under the inside-out patch recording mode, ciglitazone applied intracellularly increased the activity of the large-conductance Ca2+-activated K+ (BK(Ca)) channels, but did not affect their single-channel conductance. However, troglitazone (30 μmol/L) caused a reduction in the channel activity. The ciglitazone-induced ior of BK(Ca) channels is due to an increase in mean open time and a decrease in mean closed time, whereas the troglitazone-induced decrease in the channel activity is related to a decrease in mean open time and an increase in mean closed time. Ciglitazone caused a left shift in the midpoint for voltage-dependent opening. The ciglitazone-stimulated activity of BK(Ca) channels is independent of internal Ca2+. Under the current clamp mode, ciglitazone (30 μmol/L) hyperpolarized the membrane potential. Conclusions: This study shows that in addition to its activation of PPAR-γ, ciglitazone can stimulate the activity of BK(Ca) channels expressed in GH3 cells. These effects may affect membrane potentials and contribute to the ciglitazone-induced change in the functional activity of neurons or neuroendocrine cells.

Original languageEnglish
Pages (from-to)259-269
Number of pages11
JournalJournal of Investigative Medicine
Volume48
Issue number4
Publication statusPublished - 2000

Fingerprint

Rats
Large-Conductance Calcium-Activated Potassium Channels
troglitazone
Peroxisome Proliferators
Clamping devices
Membrane Potentials
ciglitazone
Membranes
Neuroendocrine Cells
Patch-Clamp Techniques
Hypoglycemic Agents
Neurons
Chemical activation
Electric potential

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Wu, Sheng-Nan ; Ho, L. L.T. ; Li, H. F. ; Chiang, H. T. / Regulation of Ca2+-activated K+ currents by ciglitazone in rat pituitary GH3 cells. In: Journal of Investigative Medicine. 2000 ; Vol. 48, No. 4. pp. 259-269.
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abstract = "Background: Ciglitazone, an antidiabetic agent of the thiazolidinedione family, is known to be an activator of the peroxisome-proliferator activator receptor (PPAR)-γ. The underlying mechanism of ciglitazone actions on ionic currents in neuroendocrine ceils remains unclear. Methods: The effects of ciglitazone on ionic currents were investigated in rat pituitary GH3 cells using the whole-cell and inside-out configurations of the patch-clamp technique. Results: In GH3 cells, ciglitazone at 3-300 μmol/L caused a reversible increase in the amplitude of the Ca2+-activated K+ current (I(K(Ca))) with a half-maximal concentration of 16 μmol/L. Under the inside-out patch recording mode, ciglitazone applied intracellularly increased the activity of the large-conductance Ca2+-activated K+ (BK(Ca)) channels, but did not affect their single-channel conductance. However, troglitazone (30 μmol/L) caused a reduction in the channel activity. The ciglitazone-induced ior of BK(Ca) channels is due to an increase in mean open time and a decrease in mean closed time, whereas the troglitazone-induced decrease in the channel activity is related to a decrease in mean open time and an increase in mean closed time. Ciglitazone caused a left shift in the midpoint for voltage-dependent opening. The ciglitazone-stimulated activity of BK(Ca) channels is independent of internal Ca2+. Under the current clamp mode, ciglitazone (30 μmol/L) hyperpolarized the membrane potential. Conclusions: This study shows that in addition to its activation of PPAR-γ, ciglitazone can stimulate the activity of BK(Ca) channels expressed in GH3 cells. These effects may affect membrane potentials and contribute to the ciglitazone-induced change in the functional activity of neurons or neuroendocrine cells.",
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Regulation of Ca2+-activated K+ currents by ciglitazone in rat pituitary GH3 cells. / Wu, Sheng-Nan; Ho, L. L.T.; Li, H. F.; Chiang, H. T.

In: Journal of Investigative Medicine, Vol. 48, No. 4, 2000, p. 259-269.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Regulation of Ca2+-activated K+ currents by ciglitazone in rat pituitary GH3 cells

AU - Wu, Sheng-Nan

AU - Ho, L. L.T.

AU - Li, H. F.

AU - Chiang, H. T.

PY - 2000

Y1 - 2000

N2 - Background: Ciglitazone, an antidiabetic agent of the thiazolidinedione family, is known to be an activator of the peroxisome-proliferator activator receptor (PPAR)-γ. The underlying mechanism of ciglitazone actions on ionic currents in neuroendocrine ceils remains unclear. Methods: The effects of ciglitazone on ionic currents were investigated in rat pituitary GH3 cells using the whole-cell and inside-out configurations of the patch-clamp technique. Results: In GH3 cells, ciglitazone at 3-300 μmol/L caused a reversible increase in the amplitude of the Ca2+-activated K+ current (I(K(Ca))) with a half-maximal concentration of 16 μmol/L. Under the inside-out patch recording mode, ciglitazone applied intracellularly increased the activity of the large-conductance Ca2+-activated K+ (BK(Ca)) channels, but did not affect their single-channel conductance. However, troglitazone (30 μmol/L) caused a reduction in the channel activity. The ciglitazone-induced ior of BK(Ca) channels is due to an increase in mean open time and a decrease in mean closed time, whereas the troglitazone-induced decrease in the channel activity is related to a decrease in mean open time and an increase in mean closed time. Ciglitazone caused a left shift in the midpoint for voltage-dependent opening. The ciglitazone-stimulated activity of BK(Ca) channels is independent of internal Ca2+. Under the current clamp mode, ciglitazone (30 μmol/L) hyperpolarized the membrane potential. Conclusions: This study shows that in addition to its activation of PPAR-γ, ciglitazone can stimulate the activity of BK(Ca) channels expressed in GH3 cells. These effects may affect membrane potentials and contribute to the ciglitazone-induced change in the functional activity of neurons or neuroendocrine cells.

AB - Background: Ciglitazone, an antidiabetic agent of the thiazolidinedione family, is known to be an activator of the peroxisome-proliferator activator receptor (PPAR)-γ. The underlying mechanism of ciglitazone actions on ionic currents in neuroendocrine ceils remains unclear. Methods: The effects of ciglitazone on ionic currents were investigated in rat pituitary GH3 cells using the whole-cell and inside-out configurations of the patch-clamp technique. Results: In GH3 cells, ciglitazone at 3-300 μmol/L caused a reversible increase in the amplitude of the Ca2+-activated K+ current (I(K(Ca))) with a half-maximal concentration of 16 μmol/L. Under the inside-out patch recording mode, ciglitazone applied intracellularly increased the activity of the large-conductance Ca2+-activated K+ (BK(Ca)) channels, but did not affect their single-channel conductance. However, troglitazone (30 μmol/L) caused a reduction in the channel activity. The ciglitazone-induced ior of BK(Ca) channels is due to an increase in mean open time and a decrease in mean closed time, whereas the troglitazone-induced decrease in the channel activity is related to a decrease in mean open time and an increase in mean closed time. Ciglitazone caused a left shift in the midpoint for voltage-dependent opening. The ciglitazone-stimulated activity of BK(Ca) channels is independent of internal Ca2+. Under the current clamp mode, ciglitazone (30 μmol/L) hyperpolarized the membrane potential. Conclusions: This study shows that in addition to its activation of PPAR-γ, ciglitazone can stimulate the activity of BK(Ca) channels expressed in GH3 cells. These effects may affect membrane potentials and contribute to the ciglitazone-induced change in the functional activity of neurons or neuroendocrine cells.

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