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.
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