Characterization of riluzole-induced stimulation of large-conductance calcium-activated potassium channels in rat pituitary GH3 cells

Sheng-Nan Wu; Hui Fang Li

Characterization of riluzole-induced stimulation of large-conductance calcium-activated potassium channels in rat pituitary GH₃ cells

Sheng-Nan Wu, Hui Fang Li

Institute of Basic Medical Sciences

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

Abstract

Background: Riluzole is known to be an inhibitor of glutamatergic neurotransmission. Transmitter release from nerve terminals can be regulated by the activity of large-conductance Ca²⁺-activated K⁺ (BK_Ca) channels. Methods: The ionic mechanism of actions of riluzole was investigated in neuroendocrine (GH₃ and PC12 cells), using the whole-cell patch-clamp and inside-out excised patch configurations. Results: In GH₃ cells, riluzole at 0.3-100 μmol/L increased the amplitude of Ca²⁺-activated K⁺ current (I_K(Ca)) in a concentration-dependent manner with a half maximal concentration of 5 μmol/L. The riluzole-induced increase in outward current was not be suppressed by glibenclamide (10 μmol/L) or apamin (200 nmol/L). However, iberiotoxin (200 nmol/L) or tetrandrine (10 μmol/L) can effectively suppress riluzole-induced I_K(Ca). Under inside-out patch recording mode, riluzole (10 μmol/L) applied intracellularly can increase the opening probability of large-conductance Ca²⁺-activated K⁺ (BK_Ca) channels, but did not affect their single-channel conductance. The riluzole-induced change in the kinetic behavior of BK_Ca channels is due to an increase in mean open time and a decrease in mean closed time. Riluzole caused a left shift in the midpoint for voltage-dependent opening. Riluzole-stimulated activity of BK_Ca is independent on internal Ca²⁺. Riluzole (30 μmol/L) did not affect the amplitude of voltage-dependent K⁺ current, but it produced a slight reduction of L-type voltage-dependent Ca²⁺ current. Under current clamp mode, riluzole (10 μmol/L) decreased the firing rate of action potentials induced by thyrotropin releasing hormone (10 μmol/L) in GH₃ cells. In rat pheochromocytoma PC12 cells, riluzole also increased the activity of BK_Ca channels without altering their channel conductance. Conclusion: This study shows that riluzole can stimulate the activity of BK_Ca channel in neuroendocrine cells.

Original language	English
Pages (from-to)	484-495
Number of pages	12
Journal	Journal of Investigative Medicine
Volume	47
Issue number	9
Publication status	Published - 1999 Jan 1

All Science Journal Classification (ASJC) codes

Biochemistry, Genetics and Molecular Biology(all)

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title = "Characterization of riluzole-induced stimulation of large-conductance calcium-activated potassium channels in rat pituitary GH3 cells",

abstract = "Background: Riluzole is known to be an inhibitor of glutamatergic neurotransmission. Transmitter release from nerve terminals can be regulated by the activity of large-conductance Ca2+-activated K+ (BKCa) channels. Methods: The ionic mechanism of actions of riluzole was investigated in neuroendocrine (GH3 and PC12 cells), using the whole-cell patch-clamp and inside-out excised patch configurations. Results: In GH3 cells, riluzole at 0.3-100 μmol/L increased the amplitude of Ca2+-activated K+ current (IK(Ca)) in a concentration-dependent manner with a half maximal concentration of 5 μmol/L. The riluzole-induced increase in outward current was not be suppressed by glibenclamide (10 μmol/L) or apamin (200 nmol/L). However, iberiotoxin (200 nmol/L) or tetrandrine (10 μmol/L) can effectively suppress riluzole-induced IK(Ca). Under inside-out patch recording mode, riluzole (10 μmol/L) applied intracellularly can increase the opening probability of large-conductance Ca2+-activated K+ (BKCa) channels, but did not affect their single-channel conductance. The riluzole-induced change in the kinetic behavior of BKCa channels is due to an increase in mean open time and a decrease in mean closed time. Riluzole caused a left shift in the midpoint for voltage-dependent opening. Riluzole-stimulated activity of BKCa is independent on internal Ca2+. Riluzole (30 μmol/L) did not affect the amplitude of voltage-dependent K+ current, but it produced a slight reduction of L-type voltage-dependent Ca2+ current. Under current clamp mode, riluzole (10 μmol/L) decreased the firing rate of action potentials induced by thyrotropin releasing hormone (10 μmol/L) in GH3 cells. In rat pheochromocytoma PC12 cells, riluzole also increased the activity of BKCa channels without altering their channel conductance. Conclusion: This study shows that riluzole can stimulate the activity of BKCa channel in neuroendocrine cells.",

author = "Sheng-Nan Wu and Li, {Hui Fang}",

year = "1999",

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pages = "484--495",

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T1 - Characterization of riluzole-induced stimulation of large-conductance calcium-activated potassium channels in rat pituitary GH3 cells

AU - Wu, Sheng-Nan

AU - Li, Hui Fang

PY - 1999/1/1

Y1 - 1999/1/1

N2 - Background: Riluzole is known to be an inhibitor of glutamatergic neurotransmission. Transmitter release from nerve terminals can be regulated by the activity of large-conductance Ca2+-activated K+ (BKCa) channels. Methods: The ionic mechanism of actions of riluzole was investigated in neuroendocrine (GH3 and PC12 cells), using the whole-cell patch-clamp and inside-out excised patch configurations. Results: In GH3 cells, riluzole at 0.3-100 μmol/L increased the amplitude of Ca2+-activated K+ current (IK(Ca)) in a concentration-dependent manner with a half maximal concentration of 5 μmol/L. The riluzole-induced increase in outward current was not be suppressed by glibenclamide (10 μmol/L) or apamin (200 nmol/L). However, iberiotoxin (200 nmol/L) or tetrandrine (10 μmol/L) can effectively suppress riluzole-induced IK(Ca). Under inside-out patch recording mode, riluzole (10 μmol/L) applied intracellularly can increase the opening probability of large-conductance Ca2+-activated K+ (BKCa) channels, but did not affect their single-channel conductance. The riluzole-induced change in the kinetic behavior of BKCa channels is due to an increase in mean open time and a decrease in mean closed time. Riluzole caused a left shift in the midpoint for voltage-dependent opening. Riluzole-stimulated activity of BKCa is independent on internal Ca2+. Riluzole (30 μmol/L) did not affect the amplitude of voltage-dependent K+ current, but it produced a slight reduction of L-type voltage-dependent Ca2+ current. Under current clamp mode, riluzole (10 μmol/L) decreased the firing rate of action potentials induced by thyrotropin releasing hormone (10 μmol/L) in GH3 cells. In rat pheochromocytoma PC12 cells, riluzole also increased the activity of BKCa channels without altering their channel conductance. Conclusion: This study shows that riluzole can stimulate the activity of BKCa channel in neuroendocrine cells.

AB - Background: Riluzole is known to be an inhibitor of glutamatergic neurotransmission. Transmitter release from nerve terminals can be regulated by the activity of large-conductance Ca2+-activated K+ (BKCa) channels. Methods: The ionic mechanism of actions of riluzole was investigated in neuroendocrine (GH3 and PC12 cells), using the whole-cell patch-clamp and inside-out excised patch configurations. Results: In GH3 cells, riluzole at 0.3-100 μmol/L increased the amplitude of Ca2+-activated K+ current (IK(Ca)) in a concentration-dependent manner with a half maximal concentration of 5 μmol/L. The riluzole-induced increase in outward current was not be suppressed by glibenclamide (10 μmol/L) or apamin (200 nmol/L). However, iberiotoxin (200 nmol/L) or tetrandrine (10 μmol/L) can effectively suppress riluzole-induced IK(Ca). Under inside-out patch recording mode, riluzole (10 μmol/L) applied intracellularly can increase the opening probability of large-conductance Ca2+-activated K+ (BKCa) channels, but did not affect their single-channel conductance. The riluzole-induced change in the kinetic behavior of BKCa channels is due to an increase in mean open time and a decrease in mean closed time. Riluzole caused a left shift in the midpoint for voltage-dependent opening. Riluzole-stimulated activity of BKCa is independent on internal Ca2+. Riluzole (30 μmol/L) did not affect the amplitude of voltage-dependent K+ current, but it produced a slight reduction of L-type voltage-dependent Ca2+ current. Under current clamp mode, riluzole (10 μmol/L) decreased the firing rate of action potentials induced by thyrotropin releasing hormone (10 μmol/L) in GH3 cells. In rat pheochromocytoma PC12 cells, riluzole also increased the activity of BKCa channels without altering their channel conductance. Conclusion: This study shows that riluzole can stimulate the activity of BKCa channel in neuroendocrine cells.

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Characterization of riluzole-induced stimulation of large-conductance calcium-activated potassium channels in rat pituitary GH₃ cells

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