The mechanism of inhibitory actions of S-petasin, a sesquiterpene of Petasites formosanus, on L-type calcium current in NG108-15 neuronal cells.
The effects of S-petasin, a sesquiterpene isolated from Petasites formosanus Kitamura, on ion currents in a mouse neuroblastoma and a rat glioma hybrid cell line, NG108-15, were examined with the aid of the whole-cell voltage-clamp technique. S-Petasin (1 - 300 microM) caused a decrease in the amplitude of L-type Ca2+ current (I(Ca,L)) in a concentration-dependent manner, however, it did not change the overall shape of the current-voltage relationship of I(Ca,L). The IC50 value for S-petasin-induced inhibition of I(Ca,L) was 11 microM. S-Petasin (10 microM) shifted the steady-state inactivation of I(Ca,L) to a more negative membrane potential by approximately -10 mV. S-petasin could prolong the recovery of I(Ca,L) inactivation. The inhibitory effect of S-petasin on I(Ca,L) was found to exhibit tonic and use-dependent characteristics. S-Petasin could inhibit I(Ca,L) evoked by action potential waveforms effectively. S-Petasin also suppressed low voltage-activated I(Ca,L) in NG108-15 cells. S-Petasin at a concentration of 100 microM had little effect on voltage-dependent Na+ current; however, it did produce an inhibitory effect on delayed rectifier K+ current in a time-dependent manner. These results demonstrate that S-petasin can interact directly with L-type Ca2+ channels in NG108-15 cells. These effects could contribute to the regulation of neuronal activity if similar results were found in neurons in vivo.
Wu
Sheng-Nan
SN
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan, ROC. snwu@isca.vghks.gov.tw
Chen
Hsinyo
H
Lin
Yun-Lian
YL
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005910:Glioma; D020128:Inhibitory Concentration 50; D051379:Mice; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D036901:Petasites; D008517:Phytotherapy; D051381:Rats; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D012717:Sesquiterpenes; C418727:petasin