Abstract
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 μmol/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 μmol/L) occluded Rb1-induced inhibition on VGCCs. Neither the selective N-type Ca2+ channel blocker ω-conotoxin-GVIA (1 μmol/L), nor the selective P/Q-type Ca2+ channel blocker ω-agatoxin IVA (30 nmol/L) diminished Rb1-sensitive VGCCs. Rb1 induced a leftward shift of the steady-state inactivation curve of ICa 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 μmol/L), nor by the PKA inhibitor H-89 (10 μmol/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.
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Acknowledgements
We thank Prof Shu-min DUAN (Shanghai Institute of Neuroscience, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai, China) for technical support. This work was supported by grants from the National Natural Science Foundation of China (No 30772555).
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Lin, Zy., Chen, Lm., Zhang, J. et al. Ginsenoside Rb1 selectively inhibits the activity of L-type voltage-gated calcium channels in cultured rat hippocampal neurons. Acta Pharmacol Sin 33, 438–444 (2012). https://doi.org/10.1038/aps.2011.181
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DOI: https://doi.org/10.1038/aps.2011.181
