Ginsenoside Rb1 selectively inhibits the activity of L-type voltage-gated calcium channels in cultured rat hippocampal neurons

Aim： To investigate the effect of ginsenoside Rbl on voltage-gated calcium currents in cultured rat hippocampal neurons and the modulatory mechanism. Methods： Cultured hippocampal neurons were prepared from Sprague Dawley rat embryos. Whole-cell configuration of the patch- clamp technique was used to record the voltage-gated calcium currents （VGCCs） from the hippocampal neurons, and the effect of Rbl was examined. Results： Rbl （2-100 μmol/L） inhibited VGCCs in a concentration-dependent manner, and the current was mostly recovered upon wash-out. The specific L-type Ca^2＋ channel inhibitor nifedipine （10 pmol/L） occluded Rbl-induced inhibition on VGCCs. Neither the selective N-type Ca^2＋ channel blocker ω-conotoxin-GVIA （1 pmol/L）, nor the selective P/Q-type Ca^2＋ channel blocker ω-agatoxin IVA （30 nmol/L） diminished Rbl-sensitive VGCCs. Rbl induced a leftward shift of the steady-state inactivation curve of Ica to a negative poten- tial without affecting its activation kinetics or reversal potential in the I-V curve. The inhibitory effect of Rbl was neither abolished by the adenylyl cyclase activator forskolin （10 pmol/L）, nor by the PKA inhibitor H-89 （10 pmol/L）. Conclusion： Ginsenoside Rbl selectively inhibits the activity of L-type voltage-gated calcium channels, without affecting the N-type or P/Q-type Ca^2＋ channels in hippocampal neurons, cAMP-PKA signaling pathway is not involved in this effect.