Ginsenoside Rb1 selectively inhibits the activity of L-type voltage-gated calcium channels in cultured rat hippocampal neurons
Ginsenoside Rb1 selectively inhibits the activity of L-type voltage-gated calcium channels in cultured rat hippocampal neurons
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DOI：
10.1038/aps.2011.181
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发表时间：
2012-04-01
影响因子：
8.2
通讯作者：
Chen, Xiao-chun
中科院分区：
文献类型：
--
作者：
Lin, Zhi-ying;Chen, Li-min;Chen, Xiao-chun
目的：研究人参皂苷Rb1对培养大鼠海马神经元电压门控性钙电流的影响及其调控机制。采用全细胞膜片钳技术记录海马神经元电压门控性钙电流(VGCCs)，并观察Rb1的作用。结果：Rb1(2-100mU/L)呈浓度依赖性抑制VGCCs，洗脱后电流基本恢复。特异性L钙通道阻断剂硝苯地平(10MU/L)可阻断Rb1对VGCCs的抑制作用。选择性N型钙通道阻断剂欧米茄-芋毒素-GVIA(1mU/L)和选择性P/Q型钙通道阻滞剂欧米伽-龙舌兰毒素IVA(30mU/L)均不能抑制Rb1敏感的VGCCs。Rb1使I-ca的稳态失活曲线左移至负电位，而不影响其激活动力学或I-V曲线上的反转电位。结论：人参皂苷Rb1选择性地抑制海马神经元N型和P/Q型钙通道的活动，但不能被腺苷环化酶激活剂Forsklin(10mU/L)或PKA抑制剂H-89(10mU/L)所阻断。CAMP-PKA信号通路不参与这一作用。
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.