Modulation of the Activity of Voltage-Gated Potassium Channels Kv1.3 by the Flavonols Quercetin and Morin

The aim of this study was to determine whether quercetin-mediated Kv1.3 inhibition is a general flavonol effect or compound-specific. The impact of quercetin and morin—differing by a single B-ring hydroxyl—on the endogenous Kv1.3 current in Jurkat T was compared. Currents were recorded using whole-cell patch-clamp across the 30–105 µM concentration range. Quercetin inhibited the current abruptly: no effect at 30 µM, a 40% reduction at 60 µM, followed 50% reduction in higher concentrations. Morin inhibited the current throughout the range, but its effect depended marginally on concentration. No changes in activation or inactivation kinetics were detected, and inhibition reversed upon washout. The 48 h MTT-assessed viability IC50 for quercetin was 6.25 µM, an order of magnitude below current-inhibiting concentrations, and 30.1 µM for morin. Additionally, quercetin at 30 µM, inactive alone, combined with simvastatin (6 µM), left only a quarter of the current—well below the predicted value, though exploratory testing did not establish synergy. This study reports morin’s action on Kv1.3 in Jurkat cells for the first time, showing that both flavonols inhibit the channel but that the attainable extent of inhibition is compound-specific.