Effects of the natural flavone trimethylapigenin on cardiac potassium currents

Biochem Pharmacol. 2012 Aug 15;84(4):498-506. doi: 10.1016/j.bcp.2012.05.002. Epub 2012 May 11.


The natural flavones and polymethylflavone have been reported to have cardiovascular protective effects. In the present study, we determined whether quecertin, apigenin and their methylated compounds (3,7,3',4'-tetramethylquecertin, 3,5,7,3',4'-pentamethylquecertin, 7,4'-dimethylapigenin, and 5,7,4'-trimethylapigenin) would block the atrial specific potassium channel hKv1.5 using a whole-cell patch voltage-clamp technique. We found that only trimethylapigenin showed a strong inhibitory effect on hKv1.5 channel current. This compound suppressed hKv1.5 current in HEK 293 cell line (IC₅₀=6.4 μM), and the ultra-rapid delayed rectify K⁺ current I(Kur) in human atrial myocytes (IC₅₀=8.0 μM) by binding to the open channels and showed a use- and frequency-dependent manner. In addition, trimethylapigenin decreased transient outward potassium current (I(to)) in human atrial myocytes, inhibited acetylcholine-activated K⁺ current (IC₅₀=6.8μM) in rat atrial myocytes. Interestingly, trimethylapigenin had a weak inhibition of hERG channel current. Our results indicate that trimethyapigenin significantly inhibits the atrial potassium currents hKv1.5/I(Kur) and I(KACh), which suggests that trimethylapigenin may be a potential candidate for anti-atrial fibrillation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apigenin / pharmacology*
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels / antagonists & inhibitors
  • Female
  • HEK293 Cells
  • Heart Atria / cytology
  • Humans
  • Kv1.5 Potassium Channel / antagonists & inhibitors
  • Kv1.5 Potassium Channel / physiology
  • Male
  • Myocardium / metabolism*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / physiology
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / pharmacology*
  • Potassium Channels / physiology*
  • Quercetin / analogs & derivatives
  • Quercetin / pharmacology
  • Rats
  • Rats, Sprague-Dawley


  • 3,3',4',5,7-pentamethylquercetin
  • 3,7,3',4'-O-tetramethylquercetin
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • KCNH2 protein, human
  • Kv1.5 Potassium Channel
  • Potassium Channel Blockers
  • Potassium Channels
  • 5,7,4'-trimethylapigenin
  • Apigenin
  • Quercetin