茶诱导的血管舒张作用依赖于 KCNQ5 钾通道的激活。
KCNQ5 Potassium Channel Activation Underlies Vasodilation by Tea.
机构信息
Bioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, USA.
Department of Biomedical Sciences, Vascular Biology Group, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
出版信息
Cell Physiol Biochem. 2021 Mar 6;55(S3):46-64. doi: 10.33594/000000337.
BACKGROUND/AIMS: Tea, produced from the evergreen Camellia sinensis, has reported therapeutic properties against multiple pathologies, including hypertension. Although some studies validate the health benefits of tea, few have investigated the molecular mechanisms of action. The KCNQ5 voltage-gated potassium channel contributes to vascular smooth muscle tone and neuronal M-current regulation.
METHODS
We applied electrophysiology, myography, mass spectrometry and in silico docking to determine effects and their underlying molecular mechanisms of tea and its components on KCNQ channels and arterial tone.
RESULTS
A 1% green tea extract (GTE) hyperpolarized cells by augmenting KCNQ5 activity >20-fold at resting potential; similar effects of black tea were inhibited by milk. In contrast, GTE had lesser effects on KCNQ2/Q3 and inhibited KCNQ1/E1. Tea polyphenols epicatechin gallate (ECG) and epigallocatechin-3-gallate (EGCG), but not epicatechin or epigallocatechin, isoform-selectively hyperpolarized KCNQ5 activation voltage dependence. In silico docking and mutagenesis revealed that activation by ECG requires KCNQ5-R212, at the voltage sensor foot. Strikingly, ECG and EGCG but not epicatechin KCNQ-dependently relaxed rat mesenteric arteries.
CONCLUSION
KCNQ5 activation contributes to vasodilation by tea; ECG and EGCG are candidates for future anti-hypertensive drug development.
背景/目的：茶，由常绿山茶属植物制成，据报道具有多种治疗功效，包括治疗高血压。尽管一些研究验证了茶的健康益处，但很少有研究调查其作用的分子机制。KCNQ5 电压门控钾通道有助于血管平滑肌张力和神经元 M 电流调节。
方法
我们应用电生理学、肌动描记术、质谱和计算机对接来确定茶及其成分对 KCNQ 通道和动脉张力的作用及其潜在的分子机制。
结果
1%绿茶提取物（GTE）在静息电位下通过增强 KCNQ5 活性超过 20 倍使细胞超极化；红茶的类似作用被牛奶抑制。相比之下，GTE 对 KCNQ2/Q3 的作用较小，并抑制 KCNQ1/E1。茶多酚表儿茶素没食子酸酯（ECG）和表没食子儿茶素-3-没食子酸酯（EGCG），但不是表儿茶素或表没食子儿茶素，对 KCNQ5 具有亚型选择性激活电压依赖性。计算机对接和突变显示，ECG 的激活需要 KCNQ5-R212，位于电压传感器脚。引人注目的是，ECG 和 EGCG 但不是表儿茶素，依赖 KCNQ 松弛大鼠肠系膜动脉。
结论
KCNQ5 的激活有助于茶的血管舒张；ECG 和 EGCG 是未来抗高血压药物开发的候选药物。
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