The effects of paeoniflorin monomer of a Chinese herb on cardiac ion channels

Background Because of the potential proarrhythmic effect of current antiarrhythmic drugs, it is still desirable to find safer antiarrhythmic drugs worldwide. Paeoniflorin is one of the Chinese herb monomers that have different effects on many ion channels. The present study aimed to determine the effects of paeoniflorin on cardiac ion channels. Methods Whole-cell patch-clamp technique was used to record ion channel currents. L-type calcium current (ICa-L), inward rectifier potassium current (I-K1), and transient outward potassium current (I-to1) were studied in rat ventricular myocytes and sodium current (I-Na), slow delayed rectifier current (L-Ks), and HERO current (I-Kr) were investigated in transfected human embryonic kidney 293 cells. Results One hundred mu mol/L paeoniflorin reduced the peak ICa-L by 40.29% at the test potential of +10 mV (from (-9.78 +/- 0.52) pA/pF to (-5.84 +/- 0.89) pA/pF, n=5, P=0.028). The steady-state activation curve was shifted to more positive potential in the presence of the drug. The half activation potentials were (-11.22 +/- 0.27) mV vs. (-5.95 +/- 0.84) mV (n=5, P=0.007), respectively. However, the steady-state inactivation and the time course of recovery from inactivation were not changed. One hundred mu mol/L paeoniflorin completely inhibited the peak I-Na and the effect was reversible. Moreover, paeoniflorin inhibited the I-K1, by 30.13% at the test potential of -100 mV (from (-25.26 +/- 8.21) pA/pF to (-17.65 +/- 6.52) pA/pF, n=6, P=0.015) without effects on the reversal potential and the rectification property. By contrast, 100 mu mol/L paeoniflorin had no effects on I-to1, I-Ks or I-Kr channels. Conclusions The study demonstrated that paeoniflorin blocked ICa-L, I-Na, and I-K1 without affecting I-to1, I-Ks, or I-Kr. The multi-channel block effect may account for its ptiarrhythmic effects with less proarrhythmic potential. Chin Med J 2011;124(19):3105-3111