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

Deoxyschisandrin modulates synchronized Ca2+ oscillations and spontaneous synaptic transmission of cultured hippocampal neurons
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DOI:
10.1111/j.1745-7254.2008.00821.x
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发表时间:
2008-08-01
影响因子:
8.2
通讯作者:
Xie, Zuo-Ping
Xie, Zuo-Ping
中科院分区:
医学1区
文献类型:
--
作者:
Fu, Min;Sun, Zhao-hui;Xie, Zuo-Ping

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目的:脱氧五味子素是著名中药五味子最有效的复方之一,广泛用作抗应激、抗衰老和改善神经功能的草药。在这项研究中,我们检查了其对培养的海马神经元的具体作用机制。方法:本研究使用在体外初步培养 9-11 天的海马神经元。 DS溶解在DMSO中并应用于钙成像和全细胞膜片钳。结果:应用3 mg/L DS可将细胞内Ca(2+)自发和同步振荡频率降低至72%+/- 2%(平均值+/- SEM),并将自发抑制性突触后电流降低至60%+/- 3%(平均值+/- SEM)。 DS对钙振荡影响的50%抑制浓度(IC(50))为3.8 mg/L。 DS还同时抑制了高压门控Ca(2+)通道和电压门控Na(+)通道电流。然而,它对电压门控 K(+) 和自发兴奋性突触后电流没有影响。结论:DS通过抑制细胞外钙离子内流和动作电位启动,抑制细胞内Ca(2+)自发同步振荡。通过抑制自发的神经递质释放,DS 调节神经元网络活动。
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 Ca(2+) to 72%+/- 2% (mean +/- SEM), and the spontaneous inhibitory postsynaptic currents to 60%+/- 3% (mean +/- SEM). The inhibitory concentraton 50% (IC(50)) for the effect of DS on calcium oscillations was 3.8 mg/L. DS also depressed the high voltage-gated Ca(2+) 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 Ca(2+) 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.