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白藜芦醇减弱皮层神经元活动:大电导钙激活钾通道和电压门控钠通道的作用。

Resveratrol attenuates cortical neuron activity: roles of large conductance calcium-activated potassium channels and voltage-gated sodium channels.

作者信息

Wang Ya-Jean, Chan Ming-Huan, Chen Linyi, Wu Sheng-Nan, Chen Hwei-Hisen

机构信息

Center for Neuropsychiatric Research, National Health Research Institutes, 35, Keyan Road, Zhunan, Miaoli County, 35053, Taiwan.

Institute of Neuroscience, National Chengchi University, 64, Sec.2, ZhiNan Road, Wenshan District, Taipei City, 11605, Taiwan.

出版信息

J Biomed Sci. 2016 May 21;23(1):47. doi: 10.1186/s12929-016-0259-y.

Abstract

BACKGROUND

Resveratrol, a phytoalexin found in grapes and red wine, exhibits diverse pharmacological activities. However, relatively little is known about whether resveratrol modulates the ion channels in cortical neurons. The large-conductance calcium-activated potassium channels (BKCa) and voltage-gated sodium channels were expressed in cortical neurons and play important roles in regulation of neuronal excitability. The present study aimed to determine the effects of resveratrol on BKCa currents and voltage-gated sodium currents in cortical neurons.

RESULTS

Resveratrol concentration-dependently increased the current amplitude and the opening activity of BKCa channels, but suppressed the amplitude of voltage-gated sodium currents. Similar to the BKCa channel opener NS1619, resveratrol decreased the firing rate of action potentials. In addition, the enhancing effects of BKCa channel blockers tetraethylammonium (TEA) and paxilline on action potential firing were sensitive to resveratrol. Our results indicated that the attenuation of action potential firing rate by resveratrol might be mediated through opening the BKCa channels and closing the voltage-gated sodium channels.

CONCLUSIONS

As BKCa channels and sodium channels are critical molecular determinants for seizure generation, our findings suggest that regulation of these two channels in cortical neurons probably makes a considerable contribution to the antiseizure activity of resveratrol.

摘要

背景

白藜芦醇是一种在葡萄和红酒中发现的植物抗毒素,具有多种药理活性。然而,关于白藜芦醇是否调节皮层神经元中的离子通道,人们了解相对较少。大电导钙激活钾通道(BKCa)和电压门控钠通道在皮层神经元中表达,并在调节神经元兴奋性方面发挥重要作用。本研究旨在确定白藜芦醇对皮层神经元中BKCa电流和电压门控钠电流的影响。

结果

白藜芦醇浓度依赖性地增加了BKCa通道的电流幅度和开放活性,但抑制了电压门控钠电流的幅度。与BKCa通道开放剂NS1619类似,白藜芦醇降低了动作电位的发放频率。此外,BKCa通道阻滞剂四乙铵(TEA)和青霉素对动作电位发放的增强作用对白藜芦醇敏感。我们的结果表明,白藜芦醇对动作电位发放频率的衰减可能是通过打开BKCa通道和关闭电压门控钠通道介导的。

结论

由于BKCa通道和钠通道是癫痫发作产生的关键分子决定因素,我们的研究结果表明,调节皮层神经元中的这两种通道可能对白藜芦醇的抗癫痫活性有相当大的贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5455/4875746/42e9d5cfcff6/12929_2016_259_Fig1_HTML.jpg

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