Deng Xiu-Ling, Wang Yan, Xiao Guo-Sheng
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, Fujian, China.
PLoS One. 2017 Aug 23;12(8):e0183708. doi: 10.1371/journal.pone.0183708. eCollection 2017.
The present study investigated the effects of equol on cardiovascular K+ channel currents. The cardiovascular K+ channel currents were determined in HEK 293 cells stably expressing cloned differential cardiovascular K+ channels with conventional whole-cell patch voltage-clamp technique. We found that equol inhibited hKv1.5 (IC50: 15.3 μM), hKv4.3 (IC50: 29.2 μM and 11.9 μM for hKv4.3 peak current and charge area, respectively), IKs (IC50: 24.7 μM) and IhERG (IC50: 31.6 and 56.5 μM for IhERG.tail and IhERG.step, respectively), but not hKir2.1 current, in a concentration-dependent manner. Interestingly, equol increased BKCa current with an EC50 of 0.1 μM. It had no significant effect on guinea pig ventricular action potentials at concentrations of ≤3 μM. These results demonstrate that equol inhibits several cardiac K+ currents at relatively high concentrations, whereas it increases BKCa current at very low concentrations, suggesting that equol is a safe drug candidate for treating patients with cerebral vascular disorders.
本研究调查了雌马酚对心血管钾通道电流的影响。采用传统的全细胞膜片钳电压钳技术，在稳定表达克隆的不同心血管钾通道的HEK 293细胞中测定心血管钾通道电流。我们发现，雌马酚以浓度依赖性方式抑制hKv1.5（IC50：15.3 μM）、hKv4.3（hKv4.3峰值电流和电荷面积的IC50分别为29.2 μM和11.9 μM）、IKs（IC50：24.7 μM）和IhERG（IhERG尾部和IhERG阶跃的IC50分别为31.6 μM和56.5 μM），但不抑制hKir2.1电流。有趣的是，雌马酚以0.1 μM的EC50增加BKCa电流。在浓度≤3 μM时，它对豚鼠心室动作电位没有显著影响。这些结果表明，雌马酚在相对高浓度时抑制几种心脏钾电流，而在非常低浓度时增加BKCa电流，这表明雌马酚是治疗脑血管疾病患者的安全候选药物。
