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 Rb1 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 Rb1 was examined. Results: Rb1 (2-100 mu mol/L) inhibited VGCCs in a concentration-dependent manner, and the current was mostly recovered upon wash-out. The specific L-type Ca2+ channel inhibitor nifedipine (10 mu mol/L) occluded Rb1-induced inhibition on VGCCs. Neither the selective N-type Ca2+ channel blocker omega-conotoxin-GVIA (1 mu mol/L), nor the selective P/Q-type Ca2+ channel blocker omega-agatoxin IVA (30 mu mol/L) diminished Rb1-sensitive VGCCs. Rb1 induced a leftward shift of the steady-state inactivation curve of I-ca to a negative potential without affecting its activation kinetics or reversal potential in the I-V curve. The inhibitory effect of Rb1 was neither abolished by the adenylyl cyclase activator forskolin (10 mu mol/L), nor by the PKA inhibitor H-89 (10 mu mol/L). Conclusion: Ginsenoside Rb1 selectively inhibits the activity of L-type voltage-gated calcium channels, without affecting the N-type or P/Q-type Ca2+ channels in hippocampal neurons. cAMP-PKA signaling pathway is not involved in this effect.