Inhibitory effect of the plant-extract osthole on L-type calcium current in NG108-15 neuronal cells

Sheng-Nan Wu, Yuk Kang Lo, Chien Chich Chen, Hui Fang Li, Hung Ting Chiang

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The effects of osthole, a coumarin isolated from Cnidium monnieri (L.) Cusson, on ionic currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG105-18, were investigated with the aid of the whole-cell voltage-clamp technique. Osthole (0.3-100μM) caused an inhibition of voltage-dependent L-type Ca2+ current (ICa,L) in a concentration-dependent manner. Osthole produced no change in the overall shape of the current-voltage relationship of ICa,L. The IC50 value of the osthole-induced inhibition of ICa,L was 4μM. The presence of osthole (3μM) shifted the steady state inactivation curve of ICa,L to a more negative potential by approximately -15mV. Osthole (3μM) also produced a prolongation in the recovery of ICa,L inactivation. Although osthole might suppress phosophodiesterases to increase intracellular adenosine-3′,5′-cyclic monophosphate (cyclic AMP) or guanosine-3′,5′-cyclic monophosphate (cyclic GMP), sp-cAMPS did not affect ICa,L and 8-bromo-cyclic GMP slightly suppressed it. Thus, osthole-mediated inhibition of ICa,L was not associated with intracellular cyclic AMP or GMP. However, no effect of osthole on voltage-dependent K+ outward current was observed. Under a current-clamp mode, osthole could decrease the firing frequency of action potentials. Therefore, the channel-blocking properties of osthole may, at least in part, contribute to the underlying mechanisms by which it affects neuronal or neuroendocrine function.

Original languageEnglish
Pages (from-to)199-206
Number of pages8
JournalBiochemical Pharmacology
Volume63
Issue number2
DOIs
Publication statusPublished - 2002 Jan 15

Fingerprint

Plant Extracts
Calcium
Cyclic GMP
Clamping devices
Electric potential
Cyclic AMP
Cnidium
osthol
Hybrid Cells
Guanosine
Patch-Clamp Techniques
Neuroblastoma
Glioma
Adenosine
Action Potentials
Inhibitory Concentration 50
Rats
Cells
Recovery
Cell Line

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

Cite this

Wu, Sheng-Nan ; Lo, Yuk Kang ; Chen, Chien Chich ; Li, Hui Fang ; Chiang, Hung Ting. / Inhibitory effect of the plant-extract osthole on L-type calcium current in NG108-15 neuronal cells. In: Biochemical Pharmacology. 2002 ; Vol. 63, No. 2. pp. 199-206.
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Inhibitory effect of the plant-extract osthole on L-type calcium current in NG108-15 neuronal cells. / Wu, Sheng-Nan; Lo, Yuk Kang; Chen, Chien Chich; Li, Hui Fang; Chiang, Hung Ting.

In: Biochemical Pharmacology, Vol. 63, No. 2, 15.01.2002, p. 199-206.

Research output: Contribution to journalArticle

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AU - Wu, Sheng-Nan

AU - Lo, Yuk Kang

AU - Chen, Chien Chich

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N2 - The effects of osthole, a coumarin isolated from Cnidium monnieri (L.) Cusson, on ionic currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG105-18, were investigated with the aid of the whole-cell voltage-clamp technique. Osthole (0.3-100μM) caused an inhibition of voltage-dependent L-type Ca2+ current (ICa,L) in a concentration-dependent manner. Osthole produced no change in the overall shape of the current-voltage relationship of ICa,L. The IC50 value of the osthole-induced inhibition of ICa,L was 4μM. The presence of osthole (3μM) shifted the steady state inactivation curve of ICa,L to a more negative potential by approximately -15mV. Osthole (3μM) also produced a prolongation in the recovery of ICa,L inactivation. Although osthole might suppress phosophodiesterases to increase intracellular adenosine-3′,5′-cyclic monophosphate (cyclic AMP) or guanosine-3′,5′-cyclic monophosphate (cyclic GMP), sp-cAMPS did not affect ICa,L and 8-bromo-cyclic GMP slightly suppressed it. Thus, osthole-mediated inhibition of ICa,L was not associated with intracellular cyclic AMP or GMP. However, no effect of osthole on voltage-dependent K+ outward current was observed. Under a current-clamp mode, osthole could decrease the firing frequency of action potentials. Therefore, the channel-blocking properties of osthole may, at least in part, contribute to the underlying mechanisms by which it affects neuronal or neuroendocrine function.

AB - The effects of osthole, a coumarin isolated from Cnidium monnieri (L.) Cusson, on ionic currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG105-18, were investigated with the aid of the whole-cell voltage-clamp technique. Osthole (0.3-100μM) caused an inhibition of voltage-dependent L-type Ca2+ current (ICa,L) in a concentration-dependent manner. Osthole produced no change in the overall shape of the current-voltage relationship of ICa,L. The IC50 value of the osthole-induced inhibition of ICa,L was 4μM. The presence of osthole (3μM) shifted the steady state inactivation curve of ICa,L to a more negative potential by approximately -15mV. Osthole (3μM) also produced a prolongation in the recovery of ICa,L inactivation. Although osthole might suppress phosophodiesterases to increase intracellular adenosine-3′,5′-cyclic monophosphate (cyclic AMP) or guanosine-3′,5′-cyclic monophosphate (cyclic GMP), sp-cAMPS did not affect ICa,L and 8-bromo-cyclic GMP slightly suppressed it. Thus, osthole-mediated inhibition of ICa,L was not associated with intracellular cyclic AMP or GMP. However, no effect of osthole on voltage-dependent K+ outward current was observed. Under a current-clamp mode, osthole could decrease the firing frequency of action potentials. Therefore, the channel-blocking properties of osthole may, at least in part, contribute to the underlying mechanisms by which it affects neuronal or neuroendocrine function.

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