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

TitleThe selective estrogen receptor modulator raloxifene inhibits cardiac delayed rectifier potassium currents and voltage-gated sodium current without QTc interval prolongation
Authors
Liu, HYang, LJin, MWSun, HYHuang, YLi, GR
KeywordsDelayed rectifier potassium currents
QTc interval
Raloxifene
Voltage-gated sodium current
Issue Date2010
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/issn/10436618
Citation
Pharmacological Research, 2010, v. 62 n. 5, p. 384-390 How to Cite?
DOI: http://dx.doi.org/10.1016/j.phrs.2010.07.008
AbstractRaloxifene 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 1.1μM and decreased I Ks (IC 50: 4.8μM) without affecting activation kinetics. In addition, raloxifene significantly decreased I Na (IC 50: 2.8μM) in guinea pig ventricular myocytes. However, this drug (1μM) 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. © 2010 Elsevier Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/129282
ISSN
1043-6618
2023 Impact Factor: 9.1
2023 SCImago Journal Rankings: 2.160
ISI Accession Number ID
WOS:000283407900002
Funding AgencyGrant Number
Sun Chieh Yeh Heart Foundation of Hong Kong
Funding Information:

The study was supported in part by a grant from Sun Chieh Yeh Heart Foundation of Hong Kong. The authors thank Dr. Gail Robertson for providing the hERG/pcDNA3 vector.

References
References in Scopus

 

DC FieldValueLanguage
dc.contributor.authorLiu, Hen_HK
dc.contributor.authorYang, Len_HK
dc.contributor.authorJin, MWen_HK
dc.contributor.authorSun, HYen_HK
dc.contributor.authorHuang, Yen_HK
dc.contributor.authorLi, GRen_HK
dc.date.accessioned2010-12-23T08:34:39Z-
dc.date.available2010-12-23T08:34:39Z-
dc.date.issued2010en_HK
dc.identifier.citationPharmacological Research, 2010, v. 62 n. 5, p. 384-390en_HK
dc.identifier.issn1043-6618en_HK
dc.identifier.urihttp://hdl.handle.net/10722/129282-
dc.description.abstractRaloxifene 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 1.1μM and decreased I Ks (IC 50: 4.8μM) without affecting activation kinetics. In addition, raloxifene significantly decreased I Na (IC 50: 2.8μM) in guinea pig ventricular myocytes. However, this drug (1μM) 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. © 2010 Elsevier Ltd.en_HK
dc.languageengen_US
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/issn/10436618en_HK
dc.relation.ispartofPharmacological Researchen_HK
dc.subjectDelayed rectifier potassium currentsen_HK
dc.subjectQTc intervalen_HK
dc.subjectRaloxifeneen_HK
dc.subjectVoltage-gated sodium currenten_HK
dc.subject.meshDelayed Rectifier Potassium Channels - antagonists and inhibitors - metabolism-
dc.subject.meshMyocytes, Cardiac - drug effects - metabolism-
dc.subject.meshRaloxifene - pharmacology - toxicity-
dc.subject.meshSelective Estrogen Receptor Modulators - pharmacology - toxicity-
dc.subject.meshSodium Channels - metabolism-
dc.titleThe selective estrogen receptor modulator raloxifene inhibits cardiac delayed rectifier potassium currents and voltage-gated sodium current without QTc interval prolongationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1043-6618&volume=62&issue=5&spage=384&epage=390&date=2010&atitle=The+selective+estrogen+receptor+modulator+raloxifene+inhibits+cardiac+delayed+rectifier+potassium+currents+and+voltage-gated+sodium+current+without+QTc+interval+prolongation-
dc.identifier.emailLi, GR:grli@hkucc.hku.hken_HK
dc.identifier.authorityLi, GR=rp00476en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.phrs.2010.07.008en_HK
dc.identifier.pmid20674746-
dc.identifier.scopuseid_2-s2.0-77956941034en_HK
dc.identifier.hkuros177402en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77956941034&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume62en_HK
dc.identifier.issue5en_HK
dc.identifier.spage384en_HK
dc.identifier.epage390en_HK
dc.identifier.isiWOS:000283407900002-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLiu, H=27171679500en_HK
dc.identifier.scopusauthoridYang, L=24831200200en_HK
dc.identifier.scopusauthoridJin, MW=35932258500en_HK
dc.identifier.scopusauthoridSun, HY=35723049200en_HK
dc.identifier.scopusauthoridHuang, Y=34770945300en_HK
dc.identifier.scopusauthoridLi, GR=7408462932en_HK
dc.identifier.citeulike7598307-
dc.identifier.issnl1043-6618-

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