Conclusion
Quercetin has a potential risk of proarrhythmia, which provided useful information for the usage and development of quercetin as a medication.
Methods
hERG currents and action potential duration (APD) were assessed using the patch clamp technique. Molecular docking was employed to elucidate the binding sites between quercetin and hERG. Transfection of wild-type or mutant plasmids was used to verify the
Results
Quercetin acutely blocked hERG current by binding to F656 amino acid residue, subsequently accelerating channel inactivation. Long-term incubation of quercetin accelerates Nedd4-2-mediated ubiquitination degradation of hERG channels by inhibiting the PI3K/SGK1 signaling pathway. Moreover, the APD of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) is significantly prolonged by 30 μM quercetin.