PT  - JOURNAL ARTICLE
AU  - Xiao-Hui Sun
AU  - Jiu-Ping Ding
AU  - Hui Li
AU  - Na Pan
AU  - Lu Gan
AU  - Xiang-Liang Yang
AU  - Hui-Bi Xu
TI  - Activation of Large-Conductance Calcium-Activated Potassium Channels by Puerarin: The Underlying Mechanism of Puerarin-Mediated Vasodilation
AID  - 10.1124/jpet.107.125567
DP  - 2007 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 391--397
VI  - 323
IP  - 1
4099  - http://jpet.aspetjournals.org/content/323/1/391.short
4100  - http://jpet.aspetjournals.org/content/323/1/391.full
SO  - J Pharmacol Exp Ther2007 Oct 01; 323
AB  - Puerarin is the main isoflavone found in Pueraria lobata (Willd) Ohwi, which has been used in therapy for various cardiovascular diseases. The present study examined the effects of puerarin on the large-conductance voltage- and Ca2+-activated potassium (BKCa) channel and on rat thoracic aortas. BKCa channels encoded with either α (BK-α) or α/β subunits (BK-α+β1) were heterologously expressed in Xenopus oocytes or human embryonic kidney 293 cells. The activities of BKCa channels were measured using excised patch-clamp recordings. Puerarin activated BK-α+β1 currents with a half-maximal concentration (EC50) of 0.8 nM and a Hill coefficient of 1.11 at 10 μMCa2+ and with an EC50 of 12.6 nM and a Hill coefficient of 1.08 at 0 μMCa2+. Puerarin (1 nM) induced a 16-mV leftward shift in the conductance-voltage curve for BK-α+β1 currents at 10 μMCa2+ and at 100 nM induced a 26-mV leftward shift at 0 μMCa2+. Puerarin mainly increased the BK-α+β1 channel open probability without changing the unitary conductance. Activation was also detected in the absence of the β1 subunit. A deglycosylated analog of puerarin, daidzein, also activated BKCa channels with weaker potency. In addition, puerarin (0.1 to 1000 μM) caused concentration-dependent relaxations of rat thoracic aortic rings contracted with 1 μM noradrenaline bitartrate (EC50 = 1.1 μM). These were significantly inhibited by 50 nM iberiotoxin, a specific blocker of BKCa channels. This is the first study demonstrating that puerarin activates BKCa channels, especially BK-α+β1 channels. The activation of the BKCa channel probably contributes to the puerarin-mediated vasodilation action. The American Society for Pharmacology and Experimental Therapeutics