Piceatannol, a derivative of resveratrol, moderately slows INa inactivation and exerts antiarrhythmic action in ischaemia-reperfused rat hearts

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.