Referenced in: none

Automatically associated channels: Kv1.5 , Kv11.1

Title: Effects of the natural flavone trimethylapigenin on cardiac potassium currents.

Authors: Yi Liu, Xiao-Hui Xu, Zheng Liu, Xin-Ling Du, Kui-Hao Chen, Xin Xin, Zhen-Dong Jin, Ji-Zhong Shen, Yan Hu, Gui-Rong Li, Man-Wen Jin

Journal, date & volume: Biochem. Pharmacol., 2012 Aug 15 , 84, 498-506

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22583923

Abstract
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.