Piceatannol, a derivative of resveratrol, moderately slows I(Na) inactivation and exerts antiarrhythmic action in ischaemia-reperfused rat hearts.
OBJECTIVE
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.


METHODS
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.


RESULTS
In rat ventricular cells, piceatannol (3-30 micromol.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 micromol.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 micromol.L(-1), piceatannol could inhibit I(Ca,L), I(to), I(Kr), Ca2+ transients and Na+-Ca2+ exchange except I(K1). Piceatannol (1-10 micromol.L(-1)) exerted antiarrhythmic activity in isolated rat hearts subjected to ischaemia-reperfusion injury.


CONCLUSIONS
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 micromol.L(-1).
Chen
Wen-Pin
WP
Institute of Pharmacology, National Taiwan University Medical College, Taipei 100, Taiwan.
Hung
Li-Man
LM
Hsueh
Chia-Hsiang
CH
Lai
Ling-Ping
LP
Su
Ming-Jai
MJ
D000157:Aconitine / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control*; D002110:Caffeine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology; D002460:Cell Line; D000072237:ERG1 Potassium Channel; D004558:Electric Stimulation; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000378:metabolism; D016166:Free Radical Scavengers / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000150:complications*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D062687:Sodium Channel Agonists; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000502:physiology*; D013267:Stilbenes / Q000009:adverse effects / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D016166:Free Radical Scavengers; D062687:Sodium Channel Agonists; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013267:Stilbenes; D002110:Caffeine; C041525:3,3',4,5'-tetrahydroxystilbene; D000077185:Resveratrol; D000157:Aconitine