Mechanisms of artemisinin antiarrhythmic action

The effects of artemisinin on the potassium ionic currents of guinea pig ventricular cells and dog Purkinje fibres were studied using the whole cell voltage clamp technique. Artemisinin significantly decreased inward rectifier K+ current (I(Kl)) with an IC50 of (7.2 ± 0.8) μmol·L-1 at -100 mV in guinea pig ventricular cells. The blocking effect on I(Kl) was concentration-dependent, but not frequency-dependent. In dog Purkinje fibres, artemisinin significantly inhibited the transient outward K+ current (I(to)) (decreased by 84% at 100 μmol·L-1) in a concentration-dependent manner, with an IC50 of (4.7 ± 0.3) μmol·L-1. In guinea pig ventricular cells, artemisinin at 50 μmol·L-1 decreased the delayed outward rectifier K+ current (I(K)); time-dependent outward potassium current (I(Kstep)) by (38 ± 10)% at +40 mV. The envelope of tail analysis suggested that both the rapid component (I(Kr)) and the slow component (I(Ks)) of I(k) be inhibited. These results suggest that artemisinin inhibit I(Kl), I(to) and I(K) in cardiac myocytes with similar potency, which may be related to the antiarrhythmic action of artemisinin.