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Drinking fresh grapefruit juice is associated with a significant prolongation of the QT segment on the electrocardiogram (ECG) in healthy volunteers. Among the prominent polyphenols contained in citrus fruits and primarily in grapefruit, the flavonoid naringenin is known to be a blocker of the human ether-a-go-go related gene (hERG) potassium channel. Here we hypothesized that naringenin could interfere with other major ion channels shaping the cardiac ventricular action potential (AP). To test this hypothesis, we examined the effects of naringenin on the seven channels comprising the Comprehensive in vitro Pro-Arrhythmia (CiPA) ion channel panel for early arrhythmogenic risk assessment in drug discovery and development. We used automated population patch-clamp of human ion channels heterologously expressed in mammalian cells to evaluate half-maximal inhibitory concentrations (IC 50 ). Naringenin blocked all CiPA ion channels tested with IC 50 values in the 30-100 µM concentration-range. The rank-order of channel sensitivity was the following: hERG > K ir 2.1 > Na V 1.5 (late current) > Na V 1.5 (peak current) > K V 7.1 > K V 4.3 > Ca V 1.2. This multichannel inhibitory profile of naringenin suggests exercising caution when large amounts of grapefruit juice or other citrus juices enriched in this flavonoid polyphenol are drunk in conjunction with QT prolonging drugs or by carriers of congenital long-QT syndromes., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)