The selective estrogen receptor modulator raloxifene inhibits cardiac delayed rectifier potassium currents and voltage-gated sodium current without QTc interval prolongation

Raloxifene is widely used in the treatment of postmenopausal osteoporosis and also has been shown to be cardioprotective. The effect of raloxifene on cardiac ion channels is not fully understood. The present study investigated whether raloxifene could affect the cloned hERG channel (IhERG) and recombinant human cardiac KCNQ1/KCNE1 channel (IKs) stably expressed in HEK 293 cells using a patch-clamp technique. Raloxifene blocked IhERG with an IC50 of 1.1 μM and decreased IKs (IC50: 4.8 μM) without affecting activation kinetics. In addition, raloxifene significantly decreased INa (IC50: 2.8 μM) in guinea pig ventricular myocytes. However, this drug (1 μM) did not increase QRS and QTc interval in isolated guinea pig hearts. These results demonstrate that raloxifene, despite its inhibitory action on delayed rectifier potassium currents, does not prolong ECG QTc interval, suggesting that raloxifene is likely a safe selective estrogen receptor modulator with less cardiac toxicity.

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