Inhibitory effects of hesperetin on Kv1.5 potassium channels stably expressed in HEK 293 cells and ultra-rapid delayed rectifier K(+) current in human atrial myocytes.
Inhibitory effects of hesperetin on Kv1.5 potassium channels stably expressed in HEK 293 cells and ultra-rapid delayed rectifier K(+) current in human atrial myocytes.
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DOI：
10.1016/j.ejphar.2016.07.015
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发表时间：
2016-10
影响因子：
5
通讯作者：
Huan Wang;Hong-fei Wang;Chen Wang;Yu-fang Chen;Rong Ma;Ji-zhou Xiang;Xin-ling Du;Q. Tang
中科院分区：
文献类型：
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作者：
Huan Wang;Hong-fei Wang;Chen Wang;Yu-fang Chen;Rong Ma;Ji-zhou Xiang;Xin-ling Du;Q. Tang
本研究采用膜片钳全细胞结构技术，研究了hesperetin （HSP）对人心脏HEK 293细胞表达的Kv1.5通道和人心房肌细胞超快速延迟整流K+电流（Ikur）的抑制作用。我们发现橙皮苷以浓度依赖的方式快速、可逆地抑制人Kv1.5电流，半最大抑制（IC50）为23.15 μΜ， Hill系数为0.89。当橙皮苷浓度为300 μM时，电流最大衰减约71.36%。Hesperetin对Kv1.5的稳态激活曲线有显著的正偏移，对Kv1.5的稳态失活曲线有显著的负偏移。Hesperetin也加速了Kv1.5电流的失活，并显著减缓了从失活中恢复的速度。橙皮苷阻断Kv1.5电流呈频率依赖性。然而，在移液管溶液中加入30 μM橙皮素对Kv1.5通道电流没有影响，而在细胞外施加30 μM橙皮素对电流有显著的可逆抑制作用。我们还发现hesperetin有效且可逆地抑制人心房肌细胞的超偿还延迟K+电流（Ikur），这与hesperetin对HEK 293细胞Kv1.5电流的影响一致。总之，橙皮苷是一种有效的fikur抑制剂（由Kv1.5编码），其阻断可能是由于细胞外的开放状态和失活状态通道被阻断。
In the present study, the inhibitory effects of hesperetin (HSP) on human cardiac Kv1.5 channels expressed in HEK 293 cells and the ultra-rapid delayed rectifier K+current (Ikur) in human atrial myocytes were examined by using the whole-cell configuration of the patch-clamp techniques. We found that hesperetin rapidly and reversibly suppressed human Kv1.5 current in a concentration dependent manner with a half-maximal inhibition (IC50) of 23.15 μΜ with a Hill coefficient of 0.89. The current was maximally diminished about 71.36% at a concentration of 300 μM hesperetin. Hesperetin significantly positive shifted the steady-state activation curve of Kv1.5, while negative shifted the steady-state inactivation curve. Hesperetin also accelerated the inactivation and markedly slowed the recovery from the inactivation of Kv1.5 currents. Block of Kv1.5 currents by hesperetin was in a frequency dependent manner. However, inclusion of 30 μM hesperetin in pipette solution produced no effect on Kv1.5 channel current, while the current were remarkable and reversibly inhibited by extracellular application of 30 μM hesperetin. We also found that hesperetin potently and reversibly inhibited the ultra-repaid delayed K+current (Ikur) in human atrial myocytes, which is in consistent with the effects of hesperetin on Kv1.5 currents in HEK 293 cells. In conclusion, hesperetin is a potent inhibitor ofIkur(which is encoded by Kv1.5), with blockade probably due to blocking of both open state and inactivated state channels from outside of the cell.