• The Korean Journal of Physiology and Pharmacology
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• v.15 no.5
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• pp.279-283
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• 2011

Quercetin (3,3',4',5,7-pentahydroxyflavone) is an attractive therapeutic flavonoid for cancer treatment because of its beneficial properties including apoptotic, antioxidant, and antiproliferative effects on cancer cells. However, the exact mechanism of action of quercetin on ion channel modulation is poorly understood in bladder cancer 253J cells. In this study, we demonstrated that large conductance $Ca^{2+}$-activated $K^+$ ($BK_{Ca}$) or MaxiK channels were functionally expressed in 253J cells, and quercetin increased $BK_{Ca}$ current in a concentration dependent and reversible manner using a whole cell patch configuration. The half maximal activation concentration ($IC_{50}$) of quercetin was $45.5{\pm}7.2{\mu}m$. The quercetin-evoked $BK_{Ca}$ current was inhibited by tetraethylammonium (TEA; 5 mM) a non-specific $BK_{Ca}$ blocker and iberiotoxin (IBX; 100 nM) a $BK_{Ca}$-specific blocker. Quercetin-induced membrane hyperpolarization was measured by fluorescence-activated cell sorting (FACS) with voltage sensitive dye, bis (1,3-dibutylbarbituric acid) trimethine oxonol ($DiBAC_4$2(3); 100 nM). Quercetin-evoked hyperpolarization was prevented by TEA. Quercetin produced an antiproliferative effect ($30.3{\pm}13.5%$) which was recovered to $53.3{\pm}10.5%$ and $72.9{\pm}3.7%$ by TEA and IBX, respectively. Taken together our results indicate that activation of $BK_{Ca}$ channels may be considered an important target related to the action of quercetin on human bladder cancer cells.

• Journal of Ginseng Research
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• v.23 no.4
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• pp.235-238
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• 1999

ATP-sensitive $K^+$ channels $(K_{ATP})$ are expressed in vascular smooth muscle cells, skeletal muscle cells, pancreatic ${\beta}$ cells, neurons and epithelial cells. $K_{ATP}$ contributes to regulate membrane potential to control vascular tone, to protect myocardial ischemia, and to regulate insulin secretion in pancreatic ${\beta}$ cells. We previously demonstrated that ginseng saponins and ginsenoside $Rg_3$ activated maxi $Ca^{2+}-activated\;K^+$ channel, and this might cause vasodilation. Because $K_{ATP}$ plays an important roles to regulate the resting membrane potential in vascular smooth muscle cells, we investigated whether ginsenoside $Rg_3$ produces vasodilation by activating $K_{ATP}$ We showed in this study that $K_{ATP}$ is expressed in rabbit coronary artery smooth muscle cells. $K_{ATP}$ was inwardly rectifying and was inhibited by intemal application of ATP. Micromolar minoxidil activated, but glyburide inhibited the activity of $K_{ATP}$ Ginsenoside $Rg_3$ relieved inactivaiton of whole-cell $K_{ATP}$ current without affecting the peak amplitude of $K_{ATP}$ currents presumably due to more opening of the channels.