Actions of KMUP-1, a xanthine and piperazine derivative, on voltage-gated Na+ and Ca2+-activated K+ currents in GH3 pituitary tumour cells

Yi Ching Lo, Yu Ting Tseng, Chi Ming Liu, Bin Nan Wu, Sheng-Nan Wu

研究成果: Article

7 引文 (Scopus)

摘要

Background and Purpose 7-[2-[4-(2-Chlorophenyl)piperazinyl]ethyl]-1,3-dimethylxanthine (KMUP-1) is a xanthine-based derivative. It has soluble GC activation and K+-channel opening activity. Effects of this compound on ion currents in pituitary GH3 cells were investigated in this study. Experimental Approach The aim of this study was to evaluate effects of KMUP-1 on the amplitude and gating of voltage-gated Na+ current (INa) in pituitary GH3 cells and in HEKT293T cells expressing SCN5A. Both the amplitude of Ca2+-activated K+ current and the activity of large-conductance Ca2+-activated K+ (BKCa) channels were also studied. Key Results KMUP-1 depressed the transient and late components of INa with different potencies. The IC50 values required for its inhibitory effect on transient and late INa were 22.5 and 1.8 μM respectively. KMUP-1 (3 μM) shifted the steady-state inactivation of INa to a hyperpolarized potential by -10 mV, despite inability to alter the recovery of INa from inactivation. In cell-attached configuration, KMUP-1 applied to bath increased BKCa-channel activity; however, in inside-out patches, this compound applied to the intracellular surface had no effect on it. It prolonged the latency in the generation of action currents elicited by triangular voltage ramps. Additionally, KMUP-1 decreased the peak INa with a concomitant increase of current inactivation in HEKT293T cells expressing SCN5A. Conclusions and Implications Apart from activating BKCa channels, KMUP-1 preferentially suppresses late INa. The effects of KUMP-1 on ion currents presented here constitute an underlying ionic mechanism of its actions.

原文English
頁(從 - 到)5110-5122
頁數13
期刊British Journal of Pharmacology
172
發行號21
DOIs
出版狀態Published - 2015 十一月 1

指紋

Xanthine
Pituitary Neoplasms
Ions
Calcium-Activated Potassium Channels
Architectural Accessibility
Theophylline
KMUP 1
piperazine
Baths
Inhibitory Concentration 50

All Science Journal Classification (ASJC) codes

  • Pharmacology

引用此文

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title = "Actions of KMUP-1, a xanthine and piperazine derivative, on voltage-gated Na+ and Ca2+-activated K+ currents in GH3 pituitary tumour cells",
abstract = "Background and Purpose 7-[2-[4-(2-Chlorophenyl)piperazinyl]ethyl]-1,3-dimethylxanthine (KMUP-1) is a xanthine-based derivative. It has soluble GC activation and K+-channel opening activity. Effects of this compound on ion currents in pituitary GH3 cells were investigated in this study. Experimental Approach The aim of this study was to evaluate effects of KMUP-1 on the amplitude and gating of voltage-gated Na+ current (INa) in pituitary GH3 cells and in HEKT293T cells expressing SCN5A. Both the amplitude of Ca2+-activated K+ current and the activity of large-conductance Ca2+-activated K+ (BKCa) channels were also studied. Key Results KMUP-1 depressed the transient and late components of INa with different potencies. The IC50 values required for its inhibitory effect on transient and late INa were 22.5 and 1.8 μM respectively. KMUP-1 (3 μM) shifted the steady-state inactivation of INa to a hyperpolarized potential by -10 mV, despite inability to alter the recovery of INa from inactivation. In cell-attached configuration, KMUP-1 applied to bath increased BKCa-channel activity; however, in inside-out patches, this compound applied to the intracellular surface had no effect on it. It prolonged the latency in the generation of action currents elicited by triangular voltage ramps. Additionally, KMUP-1 decreased the peak INa with a concomitant increase of current inactivation in HEKT293T cells expressing SCN5A. Conclusions and Implications Apart from activating BKCa channels, KMUP-1 preferentially suppresses late INa. The effects of KUMP-1 on ion currents presented here constitute an underlying ionic mechanism of its actions.",
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Actions of KMUP-1, a xanthine and piperazine derivative, on voltage-gated Na+ and Ca2+-activated K+ currents in GH3 pituitary tumour cells. / Lo, Yi Ching; Tseng, Yu Ting; Liu, Chi Ming; Wu, Bin Nan; Wu, Sheng-Nan.

於: British Journal of Pharmacology, 卷 172, 編號 21, 01.11.2015, p. 5110-5122.

研究成果: Article

TY - JOUR

T1 - Actions of KMUP-1, a xanthine and piperazine derivative, on voltage-gated Na+ and Ca2+-activated K+ currents in GH3 pituitary tumour cells

AU - Lo, Yi Ching

AU - Tseng, Yu Ting

AU - Liu, Chi Ming

AU - Wu, Bin Nan

AU - Wu, Sheng-Nan

PY - 2015/11/1

Y1 - 2015/11/1

N2 - Background and Purpose 7-[2-[4-(2-Chlorophenyl)piperazinyl]ethyl]-1,3-dimethylxanthine (KMUP-1) is a xanthine-based derivative. It has soluble GC activation and K+-channel opening activity. Effects of this compound on ion currents in pituitary GH3 cells were investigated in this study. Experimental Approach The aim of this study was to evaluate effects of KMUP-1 on the amplitude and gating of voltage-gated Na+ current (INa) in pituitary GH3 cells and in HEKT293T cells expressing SCN5A. Both the amplitude of Ca2+-activated K+ current and the activity of large-conductance Ca2+-activated K+ (BKCa) channels were also studied. Key Results KMUP-1 depressed the transient and late components of INa with different potencies. The IC50 values required for its inhibitory effect on transient and late INa were 22.5 and 1.8 μM respectively. KMUP-1 (3 μM) shifted the steady-state inactivation of INa to a hyperpolarized potential by -10 mV, despite inability to alter the recovery of INa from inactivation. In cell-attached configuration, KMUP-1 applied to bath increased BKCa-channel activity; however, in inside-out patches, this compound applied to the intracellular surface had no effect on it. It prolonged the latency in the generation of action currents elicited by triangular voltage ramps. Additionally, KMUP-1 decreased the peak INa with a concomitant increase of current inactivation in HEKT293T cells expressing SCN5A. Conclusions and Implications Apart from activating BKCa channels, KMUP-1 preferentially suppresses late INa. The effects of KUMP-1 on ion currents presented here constitute an underlying ionic mechanism of its actions.

AB - Background and Purpose 7-[2-[4-(2-Chlorophenyl)piperazinyl]ethyl]-1,3-dimethylxanthine (KMUP-1) is a xanthine-based derivative. It has soluble GC activation and K+-channel opening activity. Effects of this compound on ion currents in pituitary GH3 cells were investigated in this study. Experimental Approach The aim of this study was to evaluate effects of KMUP-1 on the amplitude and gating of voltage-gated Na+ current (INa) in pituitary GH3 cells and in HEKT293T cells expressing SCN5A. Both the amplitude of Ca2+-activated K+ current and the activity of large-conductance Ca2+-activated K+ (BKCa) channels were also studied. Key Results KMUP-1 depressed the transient and late components of INa with different potencies. The IC50 values required for its inhibitory effect on transient and late INa were 22.5 and 1.8 μM respectively. KMUP-1 (3 μM) shifted the steady-state inactivation of INa to a hyperpolarized potential by -10 mV, despite inability to alter the recovery of INa from inactivation. In cell-attached configuration, KMUP-1 applied to bath increased BKCa-channel activity; however, in inside-out patches, this compound applied to the intracellular surface had no effect on it. It prolonged the latency in the generation of action currents elicited by triangular voltage ramps. Additionally, KMUP-1 decreased the peak INa with a concomitant increase of current inactivation in HEKT293T cells expressing SCN5A. Conclusions and Implications Apart from activating BKCa channels, KMUP-1 preferentially suppresses late INa. The effects of KUMP-1 on ion currents presented here constitute an underlying ionic mechanism of its actions.

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