Synergistic inhibition of delayed rectifier K + and voltage-gated Na + currents by artemisinin in pituitary tumor (GH 3 ) cells

Edmund Cheung So, Sheng-Nan Wu, Ping-Ching Wu, Hui Zhen Chen, Chia Jung Yang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Artemisinin (ART) is an anti-malarial agent reported to influence endocrine function. Methods: Effects of ART on ionic currents and action potentials (APs) in pituitary tumor (GH 3 ) cells were evaluated by patch clamp techniques. Results: ART inhibited the amplitude of delayed-rectifier K + current (I K(DR) ) in response to membrane depolarization and accelerated the process of current inactivation. It exerted an inhibitory effect on I K(DR) with an IC 50 value of 11.2 μM and enhanced I K(DR) inactivation with a K D value of 14.7 μM. The steady-state inactivation curve of I K(DR) was shifted to hyperpolarization by 10 mV. Pretreatment of chlorotoxin (1 μM) or iloprost (100 nM) did not alter the magnitude of ART-induced inhibition of I K(DR) in GH 3 cells. ART also decreased the peak amplitude of voltage-gated Na + current (I Na ) with a concentration-dependent slowing in inactivation rate. Application of KMUP-1, an inhibitor of late I Na , was effective at reversing ART-induced prolongation in inactivation time constant of I Na . Under current-clamp recordings, ART alone reduced the amplitude of APs and prolonged the duration of APs. Conclusion: Under ART exposure, the inhibitory actions on both I K(DR) and I Na could be a potential mechanisms through which this drug influences membrane excitability of endocrine or neuroendocrine cells appearing in vivo.

Original languageEnglish
Pages (from-to)2053-2066
Number of pages14
JournalCellular Physiology and Biochemistry
Volume41
Issue number5
DOIs
Publication statusPublished - 2017 Jun 1

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Pituitary Neoplasms
Action Potentials
Iloprost
Neuroendocrine Cells
Endocrine Cells
Membranes
artemisinine
Antimalarials
Patch-Clamp Techniques
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

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title = "Synergistic inhibition of delayed rectifier K + and voltage-gated Na + currents by artemisinin in pituitary tumor (GH 3 ) cells",
abstract = "Background: Artemisinin (ART) is an anti-malarial agent reported to influence endocrine function. Methods: Effects of ART on ionic currents and action potentials (APs) in pituitary tumor (GH 3 ) cells were evaluated by patch clamp techniques. Results: ART inhibited the amplitude of delayed-rectifier K + current (I K(DR) ) in response to membrane depolarization and accelerated the process of current inactivation. It exerted an inhibitory effect on I K(DR) with an IC 50 value of 11.2 μM and enhanced I K(DR) inactivation with a K D value of 14.7 μM. The steady-state inactivation curve of I K(DR) was shifted to hyperpolarization by 10 mV. Pretreatment of chlorotoxin (1 μM) or iloprost (100 nM) did not alter the magnitude of ART-induced inhibition of I K(DR) in GH 3 cells. ART also decreased the peak amplitude of voltage-gated Na + current (I Na ) with a concentration-dependent slowing in inactivation rate. Application of KMUP-1, an inhibitor of late I Na , was effective at reversing ART-induced prolongation in inactivation time constant of I Na . Under current-clamp recordings, ART alone reduced the amplitude of APs and prolonged the duration of APs. Conclusion: Under ART exposure, the inhibitory actions on both I K(DR) and I Na could be a potential mechanisms through which this drug influences membrane excitability of endocrine or neuroendocrine cells appearing in vivo.",
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Synergistic inhibition of delayed rectifier K + and voltage-gated Na + currents by artemisinin in pituitary tumor (GH 3 ) cells . / So, Edmund Cheung; Wu, Sheng-Nan; Wu, Ping-Ching; Chen, Hui Zhen; Yang, Chia Jung.

In: Cellular Physiology and Biochemistry, Vol. 41, No. 5, 01.06.2017, p. 2053-2066.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Synergistic inhibition of delayed rectifier K + and voltage-gated Na + currents by artemisinin in pituitary tumor (GH 3 ) cells

AU - So, Edmund Cheung

AU - Wu, Sheng-Nan

AU - Wu, Ping-Ching

AU - Chen, Hui Zhen

AU - Yang, Chia Jung

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Background: Artemisinin (ART) is an anti-malarial agent reported to influence endocrine function. Methods: Effects of ART on ionic currents and action potentials (APs) in pituitary tumor (GH 3 ) cells were evaluated by patch clamp techniques. Results: ART inhibited the amplitude of delayed-rectifier K + current (I K(DR) ) in response to membrane depolarization and accelerated the process of current inactivation. It exerted an inhibitory effect on I K(DR) with an IC 50 value of 11.2 μM and enhanced I K(DR) inactivation with a K D value of 14.7 μM. The steady-state inactivation curve of I K(DR) was shifted to hyperpolarization by 10 mV. Pretreatment of chlorotoxin (1 μM) or iloprost (100 nM) did not alter the magnitude of ART-induced inhibition of I K(DR) in GH 3 cells. ART also decreased the peak amplitude of voltage-gated Na + current (I Na ) with a concentration-dependent slowing in inactivation rate. Application of KMUP-1, an inhibitor of late I Na , was effective at reversing ART-induced prolongation in inactivation time constant of I Na . Under current-clamp recordings, ART alone reduced the amplitude of APs and prolonged the duration of APs. Conclusion: Under ART exposure, the inhibitory actions on both I K(DR) and I Na could be a potential mechanisms through which this drug influences membrane excitability of endocrine or neuroendocrine cells appearing in vivo.

AB - Background: Artemisinin (ART) is an anti-malarial agent reported to influence endocrine function. Methods: Effects of ART on ionic currents and action potentials (APs) in pituitary tumor (GH 3 ) cells were evaluated by patch clamp techniques. Results: ART inhibited the amplitude of delayed-rectifier K + current (I K(DR) ) in response to membrane depolarization and accelerated the process of current inactivation. It exerted an inhibitory effect on I K(DR) with an IC 50 value of 11.2 μM and enhanced I K(DR) inactivation with a K D value of 14.7 μM. The steady-state inactivation curve of I K(DR) was shifted to hyperpolarization by 10 mV. Pretreatment of chlorotoxin (1 μM) or iloprost (100 nM) did not alter the magnitude of ART-induced inhibition of I K(DR) in GH 3 cells. ART also decreased the peak amplitude of voltage-gated Na + current (I Na ) with a concentration-dependent slowing in inactivation rate. Application of KMUP-1, an inhibitor of late I Na , was effective at reversing ART-induced prolongation in inactivation time constant of I Na . Under current-clamp recordings, ART alone reduced the amplitude of APs and prolonged the duration of APs. Conclusion: Under ART exposure, the inhibitory actions on both I K(DR) and I Na could be a potential mechanisms through which this drug influences membrane excitability of endocrine or neuroendocrine cells appearing in vivo.

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