Piceatannol, a derivative of resveratrol, moderately slows INa inactivation and exerts antiarrhythmic action in ischaemia-reperfused rat hearts
Piceatannol, a derivative of resveratrol, moderately slows INa inactivation and exerts antiarrhythmic action in ischaemia-reperfused rat hearts
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DOI：
10.1111/j.1476-5381.2008.00106.x
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发表时间：
2009-06-01
影响因子：
7.3
通讯作者：
Su, Ming-Jai
中科院分区：
文献类型：
--
作者：
Chen, Wen-Pin;Hung, Li-Man;Su, Ming-Jai
在缺血再灌注大鼠心脏中，白藜芦醇比白藜芦醇更有效地清除自由基，并具有抗心律失常和心脏保护活性。采用全细胞膜片钳技术记录大鼠心肌细胞动作电位和膜电流，研究了云杉烷醇的抗心肌缺血作用及其离子机制。Fluo-3荧光法用于测量细胞Ca 2+瞬变。在离体Langendorff灌流的大鼠心脏中，观察到云杉醇（3-30 μ mol·L ~（-1））延长大鼠心室肌细胞动作电位时程（APD），降低最大上升速率（V-max），而不改变Ca ~（2+）瞬变。白藜芦醇降低I-Na峰，减慢I-Na失活，而不是诱导持续的非失活电流，这可以被利多卡因逆转。白藜芦醇（100 μ mol.L-1）降低峰值I-Na而不减缓I-Na失活。峰值I-Na或V-max的抑制与电压依赖性稳态I-Na失活曲线的负移相关，而不改变激活阈值。当浓度大于30 μ mol·L ~（-1）时，除I-K_1外，Piceatannol对I-Ca、I-L、I-to、I-Kr、Ca ~（2+）瞬变和Na ~+-Ca ~（2+）交换均有抑制作用。1-10 μ mol·L ~（-1）的白藜芦醇对离体大鼠心肌缺血再灌注损伤有明显的抗心律失常作用，白藜芦醇上的羟基使白藜芦醇具有更强的抑制I-Na和独特的减缓I-Na失活的作用，这可能是白藜芦醇在低于10 μ mol·L ~（-1）的低浓度下具有抗心律失常作用的原因。
Piceatannol is more potent than resveratrol in free radical scavenging in association with antiarrhythmic and cardioprotective activities in ischaemic-reperfused rat hearts. The present study aimed to investigate the antiarrhythmic efficacy and the underlying ionic mechanisms of piceatannol in rat hearts.Action potentials and membrane currents were recorded by the whole-cell patch clamp techniques. Fluo-3 fluorimetry was used to measure cellular Ca2+ transients. Antiarrhythmic activity was examined from isolated Langendorff-perfused rat hearts.In rat ventricular cells, piceatannol (3-30 mu mol.L-1) prolonged the action potential durations (APDs) and decreased the maximal rate of upstroke (V-max) without altering Ca2+ transients. Piceatannol decreased peak I-Na and slowed I-Na inactivation, rather than induced a persistent non-inactivating current, which could be reverted by lidocaine. Resveratrol (100 mu mol.L-1) decreased peak I-Na without slowing I-Na inactivation. The inhibition of peak I-Na or V-max was associated with a negative shift of the voltage-dependent steady-state I-Na inactivation curve without altering the activation threshold. At the concentrations more than 30 mu mol.L-1, piceatannol could inhibit I-Ca,I-L, I-to, I-Kr, Ca2+ transients and Na+-Ca2+ exchange except I-K1. Piceatannol (1-10 mu mol.L-1) exerted antiarrhythmic activity in isolated rat hearts subjected to ischaemia-reperfusion injury.The additional hydroxyl group on resveratrol makes piceatannol possessing more potent in I-Na inhibition and uniquely slowing I-Na inactivation, which may contribute to its antiarrhythmic actions at low concentrations less than 10 mu mol.L-1.