Abstract
Tanshinone IIA, one of the main active components from Chinese herb Danshen, is widely used to treat cardiovascular diseases including arrhythmia in Asian countries especially in China. However, the mechanisms underlying its anti-arrythmia effects are not clear. In this study we investigate the effects of tanshinone IIA on human KCNQ1/KCNE1 potassium channels ( I Ks), human ether-a-go-go-related gene potassium channels (hERG), Kv1.5 potassium channels, inward rectifier potassium channels ( I K1) expressed in HEK 293 cells using patch clamp technique. Tanshinone IIA potently and reversibly enhanced the amplitude of I Ks in a concentration dependent manner with an EC 50 of 64.5 μM, accelerated the activation rate of I Ks channels, decelerated their deactivation and shifted the voltage dependence of I Ks activation to negative direction. Isoproteronol, a stimulator of β-adrenergic receptor, at 1 μM and sodium nitroprusside (SNP), a NO donor, at 1 mM, had no significant effects on the enhancement of I Ks by 30 μM tanshinone IIA. N-[2-( p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H89), a selective protein kinase A inhibitor, at 0.1 μM and 1 H-(1,2,4)oxadiazolo(4,3- a)quinoxalin-1-one (ODQ), a selective nitric oxide-sensitive guanylyl cyclase inhibitor, at 10 μM, also had no significant effects on the enhancement of I Ks by 30 μM tanshinone IIA. Tanshinone IIA did not affect expressed hERG channels, Kv1.5 channels and I K1 channels. These results indicate that tanshinone IIA directly and specifically activate human cardiac KCNQ1/KCNE1 potassium channels ( I Ks) in HEK 293 cell through affecting the channels' kinetics.
Published Version
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