Inhibitory effect of the plant-extract osthole on L-type calcium current in NG108-15 neuronal cells.
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.
Wu
Sheng Nan
SN
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
Lo
Yuk Kang
YK
Chen
Chien Chich
CC
Li
Hui Fang
HF
Chiang
Hung Ting
HT
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
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