Activation of Large-Conductance Calcium-Activated Potassium Channels by Puerarin: The Underlying Mechanism of Puerarin-Mediated Vasodilation

• Published in: The Journal of pharmacology and experimental therapeutics 2007-10, Vol.323 (1), p.391-397
• Main Authors: Sun, Xiao-Hui, Ding, Jiu-Ping, Li, Hui, Pan, Na, Gan, Lu, Yang, Xiang-Liang, Xu, Hui-Bi
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Animals; Aorta, Thoracic - drug effects; Cell Line; Dose-Response Relationship, Drug; Humans; In Vitro Techniques; Isoflavones - pharmacology; Large-Conductance Calcium-Activated Potassium Channels - biosynthesis; Large-Conductance Calcium-Activated Potassium Channels - metabolism; Male; Oocytes - metabolism; Patch-Clamp Techniques; Potassium Channel Blockers - pharmacology; Rats; Rats, Wistar; Vasodilation - drug effects; Vasodilator Agents - pharmacology; Xenopus laevis
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.107.125567

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 Ca 2+ -activated potassium (BK Ca ) channel and on rat thoracic aortas. BK Ca 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 BK Ca channels were measured using excised patch-clamp recordings. Puerarin activated BK-α+β1 currents with a half-maximal concentration (EC 50 ) of 0.8 nM and a Hill coefficient of 1.11 at 10 μMCa 2+ and with an EC 50 of 12.6 nM and a Hill coefficient of 1.08 at 0 μMCa 2+ . Puerarin (1 nM) induced a 16-mV leftward shift in the conductance-voltage curve for BK-α+β1 currents at 10 μMCa 2+ and at 100 nM induced a 26-mV leftward shift at 0 μMCa 2+ . 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 BK Ca 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 (EC 50 = 1.1 μM). These were significantly inhibited by 50 nM iberiotoxin, a specific blocker of BK Ca channels. This is the first study demonstrating that puerarin activates BK Ca channels, especially BK-α+β1 channels. The activation of the BK Ca channel probably contributes to the puerarin-mediated vasodilation action.