Liposomal quercetin potentiates maxi-K channel openings in smooth muscles and restores its activity after oxidative stress

The effects of quercetin-loaded liposomes (PCL-Q) and their constituents, that is, free quercetin (Q) and ‘empty’ phosphatidylcholine vesicles (PCL), on maxi-K channel activity were studied in single mouse ileal myocytes before and after H₂O₂-induced oxidative stress. Macroscopic Maxi-K channel currents were recorded using whole-cell patch clamp techniques, while single BK_Ca channel currents were recorded in the cell-attached configuration. Bath application of PCL-Q (100?μg/ml of lipid and 3?μg/ml of quercetin) increased single Maxi-K channel activity more than threefold, from 0.010?±?0.003 to 0.034?±?0.004 (n?=?5; p?<?0.05), whereas single-channel conductance increased non-significantly from 138 to 146?pS. In the presence of PCL-Q multiple simultaneous channel openings were observed, with up to eight active channels in the membrane patch. Surprisingly, ‘empty’ PCL (100?μg/ml) also produced some channel activation, although it was less potent compared to PCL-Q, that is, these increased NPo from 0.010?±?0.003 to 0.019?±?0.003 (n?=?5; p?<?0.05) and did not affect single-channel conductance (139?pS). Application of PCL-Q restored macroscopic Maxi-K currents suppressed by H₂O₂-induced oxidative stress in ileal smooth muscle cells. We conclude that PCL-Q can activate Maxi-K channels in ileal myocytes mainly by increasing channel open probability, as well as maintain Maxi-K-mediated whole-cell current under the conditions of oxidative stress. While fusion of the ‘pure’ liposomes with the plasma membrane may indirectly activate Maxi-K channels by altering channel’s phospholipids environment, the additional potentiating action of quercetin may be due to its better bioavailability.