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 (I(hERG)) and recombinant human cardiac KCNQ1/KCNE1 channel (I(Ks)) stably expressed in HEK 293 cells using a patch-clamp technique. Raloxifene blocked I(hERG) with an IC(50) of 1.1 μM and decreased I(Ks) (IC(50): 4.8 μM) without affecting activation kinetics. In addition, raloxifene significantly decreased I(Na) (IC(50): 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.
Liu
Hui
H
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yang
Lei
L
Jin
Man-Wen
MW
Sun
Hai-Ying
HY
Huang
Yu
Y
Li
Gui-Rong
GR
D000818:Animals; D051668:Delayed Rectifier Potassium Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004562:Electrocardiography; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D057809:HEK293 Cells; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000037:antagonists & inhibitors / Q000378:metabolism; D008133:Long QT Syndrome / Q000139:chemically induced; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000378:metabolism; D020849:Raloxifene Hydrochloride / Q000494:pharmacology* / Q000633:toxicity; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology* / Q000633:toxicity; D012727:Sex Characteristics; D015222:Sodium Channels / Q000378:metabolism*
D051668:Delayed Rectifier Potassium Channels; D051638:Ether-A-Go-Go Potassium Channels; C489622:KCNE1 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D024642:Potassium Channels, Voltage-Gated; D020845:Selective Estrogen Receptor Modulators; D015222:Sodium Channels; D020849:Raloxifene Hydrochloride