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.