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五味子甲素调节培养海马神经元的同步钙离子振荡和自发性突触传递。

Deoxyschisandrin modulates synchronized Ca2+ oscillations and spontaneous synaptic transmission of cultured hippocampal neurons.

作者信息

Fu Min, Sun Zhao-hui, Zong Min, He Xiang-ping, Zuo Huan-cong, Xie Zuo-ping

机构信息

Medical College of Tsinghua University, Beijing 100084, China.

出版信息

Acta Pharmacol Sin. 2008 Aug;29(8):891-8. doi: 10.1111/j.1745-7254.2008.00821.x.

Abstract

AIM

Deoxyschisandrin is one of the most effective composites of Schisandra chinensis, a famous Chinese medicine widely used as an antistress, anti-aging, and neurological performance-improving herb. In this study, we examined its specific mechanisms of action on cultured hippocampal neurons.

METHODS

Hippocampal neurons, primarily cultured for 9-11 d in vitro, were used for this study. DS were dissolved in DMSO and applied to calcium imaging and whole-cell patch clamp.

RESULTS

The application of 3 mg/L DS decreased the frequency of spontaneous and synchronous oscillations of intracellular Ca2+ to 72%+/-2% (mean+/-SEM), and the spontaneous inhibitory postsynaptic currents to 60%+/-3% (mean+/-SEM). The inhibitory concentration 50% (IC50) for the effect of DS on calcium oscillations was 3.8 mg/L. DS also depressed the high voltage-gated Ca2+ channel and the voltage-gated Na+ channel currents at the same time point. It had no effect, however, on voltage-gated K+ and spontaneous excitatory postsynaptic currents.

CONCLUSION

DS inhibited the spontaneous and synchronous oscillations of intracellular Ca2+ through the depression of influx of extracellular calcium and the initiation of action potential. By repressing the spontaneous neurotransmitter release, DS modulated the neuronal network activities.

摘要

目的

五味子醇甲是五味子最有效的成分之一,五味子是一种著名的中药,广泛用作抗应激、抗衰老和改善神经功能的草药。在本研究中,我们研究了其对培养的海马神经元的具体作用机制。

方法

本研究使用体外原代培养9 - 11天的海马神经元。五味子醇甲溶解于二甲基亚砜中,并应用于钙成像和全细胞膜片钳实验。

结果

应用3 mg/L五味子醇甲可使细胞内Ca2+的自发同步振荡频率降低至72%±2%(平均值±标准误),自发抑制性突触后电流降低至60%±3%(平均值±标准误)。五味子醇甲对钙振荡作用的半数抑制浓度(IC50)为3.8 mg/L。在同一时间点,五味子醇甲还同时抑制了高电压门控Ca2+通道和电压门控Na+通道电流。然而,它对电压门控K+通道和自发兴奋性突触后电流没有影响。

结论

五味子醇甲通过抑制细胞外钙内流和动作电位的产生,抑制细胞内Ca2+的自发同步振荡。通过抑制自发神经递质释放,五味子醇甲调节神经元网络活动。

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