title: Inhibitory effect of the plant-extract osthole on L-type calcium current in NG108-15 neuronal cells.
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 (0.3-100 microM) caused an inhibition of voltage-dependent L-type Ca(2+) current (I(Ca,L)) in a concentration-dependent manner. Osthole produced no change in the overall shape of the current-voltage relationship of I(Ca,L). The IC(50) value of the osthole-induced inhibition of I(Ca,L) was 4 microM. The presence of osthole (3 microM) shifted the steady state inactivation curve of I(Ca,L) to a more negative potential by approximately -15mV. Osthole (3 microM) also produced a prolongation in the recovery of I(Ca,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 I(Ca,L) and 8-bromo-cyclic GMP slightly suppressed it. Thus, osthole-mediated inhibition of I(Ca,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.
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st Road, 813, ROC, Kaohsiung City, Taiwan. snwu@isca.vghks.gov.tw
authors.forename: Sheng Nan
authors.initials: SN
authors.lastname: Wu
authors.forename: Yuk Kang
authors.initials: YK
authors.lastname: Lo
authors.forename: Chien Chich
authors.initials: CC
authors.lastname: Chen
authors.forename: Hui Fang
authors.initials: HF
authors.lastname: Li
authors.forename: Hung Ting
authors.initials: HT
authors.lastname: Chiang
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D003374:Coumarins / Q000494:pharmacology*; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D006822:Hybrid Cells; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009553:Nimodipine / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology; D051381:Rats; D013873:Thionucleotides / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D003374:Coumarins; D024642:Potassium Channels, Voltage-Gated; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; C016276:8-bromocyclic GMP; D009553:Nimodipine; D020866:omega-Conotoxin GVIA; D000242:Cyclic AMP; D006152:Cyclic GMP; C046627:osthol