白藜芦醇甙对大鼠心室乳头状肌动作电位的影响及其离子机制(英文)

Effect of polydatin on action potential in ventricular papillary muscle of rat and the underlying ionic mechanism

有研究表明白藜芦醇甙(polydatin)具有抗缺血性心律失常作用,但其电生理学机制尚未明了。本研究旨在应用细胞内记录和全细胞膜片钳方法,探讨白藜芦醇甙对大鼠心室乳头状肌动作电位的影响及其离子机制。结果显示:(1)白藜芦醇甙(50和100μmol/L)可剂量依赖性地缩短正常乳头状肌动作电位复极化50%时间(APD50)和90%时间(APD90)(P<0.01)。白藜芦醇甙对正常乳头状肌静息电位(resting potential,RP)、动作电位幅值(amplitude of action potential,APA)、超射值(overshoot,OS)和0期最大上升速度(Vmax)无影响(P>0.05)。(2)对部分去极化的乳头状肌,白藜芦醇甙(50μmol/L)不但缩短APD50和APD90,而且还降低动作电位OS、APA和Vmax(P<0.05)。(3)ATP敏感钾通道阻断剂格列本脲(10μmol/L)可部分阻断白藜芦醇甙(50μmol/L)的电生理效应。(4)一氧化氮合酶抑制剂L-NAME(1 mmol/L)对白藜芦醇甙的上述效应无影响。(5)白藜芦醇甙(25、50、75、100μmol/L)可浓度依赖性降低L-型钙电流。(6)白藜芦醇甙(50μmol/L)可增加ATP敏感钾电流。以上结果提示,白藜芦醇甙可浓度依赖性缩短正常乳头状肌动作电位复极化过程,抑制部分去极化乳头状肌动作电位,此作用与L-型钙通道阻断、ATP敏感钾通道开放有关。

It is proved that polydatin has cardioprotection against ischemia-induced arrhythmia,but the electrophysiological mechanism is not clear.The aim of the present study was to investigate the effect of polydatin on action potential（AP） in ventricular papillary muscle and the underlying ionic mechanism in rat using intracellular recording and whole-cell patch clamp techniques.The results showed：（1） In normal papillary muscles,polydatin（50 and 100 μmol/L） shortened duration of 50% repolarization（APD50） and duration of 90% repolarization（APD90） in a concentration-dependent manner（P〈0.01）.But polydatin had no effects on resting potential（RP）,overshoot（OS）,amplitude of action potential（APA） and maximal rate of depolarization in phase 0（Vmax） in normal papillary muscles（P〉0.05）.（2） In partially depolarized papillary muscles,polydatin（50 μmol/L） not only shortened APD50 and APD90（P〈0.05）,but also decreased OS,APA and Vmax（P〈0.05）.（3） After pretreatment with glibenclamide（10 μmol/L）,an ATP-sensitive K^＋ channel blocker,the electrophysiological effect of polydatin（50 μmol/L） was partially inhibited.（4） Pretreatment with N^G-nitro-L-arginine methyl ester（L-NAME,1 mmol/L）,a nitric oxide（NO） synthase inhibitor,failed to abolish the effect of polydatin（50 μmol/L） on AP.（5） Polydatin（25,50,75 and 100 μmol/L） decreased L-type Ca^2＋ current in ventricular myocytes in a concentration-dependent manner（P〈0.05）.（6） Polydatin（50 μmol/L） increased ATP-sensitive K^＋ current in ventricular myocytes（P〈0.05）.The results suggest that polydatin can shorten the repolarization of AP in normal papillary muscle and inhibit AP in partially depolarized papillary muscle,which might be related to the blocking of L-type Ca^2＋ channel and the opening of ATP-sensitive K^＋ channel.