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Article: Raloxifene inhibits transient outward and ultra-rapid delayed rectifier potassium currents in human atrial myocytes

TitleRaloxifene inhibits transient outward and ultra-rapid delayed rectifier potassium currents in human atrial myocytes
Authors
Issue Date2007
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ejphar
Citation
European Journal Of Pharmacology, 2007, v. 563 n. 1-3, p. 61-68 How to Cite?
AbstractThe selective estrogen receptor modulator raloxifene is widely used in the treatment of postmenopausal osteoporosis, and has cardioprotective properties. However, effects of raloxifene on cardiac ion channels are unclear. The present study was designed to investigate the effects of raloxifene and β-estradiol on transient outward and ultra-rapid delayed rectifier potassium currents (Ito1 and IKur) in human atrial myocytes with a whole cell patch-clamp technique. Ito1 was inhibited by raloxifene in a concentration-dependent manner with an IC50 of 0.9 μM. Raloxifene at 1 μM decreased Ito1 by 40.2 ± 1.9% (at + 50 mV, n = 14, P < 0.01 vs control). Time-dependent recovery from inactivation was slowed, and time to peak and time-dependent inactivation of Ito1 were significantly accelerated, while steady-state voltage dependent activation and inactivation of Ito1 were not affected by raloxifene. In addition, raloxifene remarkably suppressed IKur (IC50 = 0.7 μM). Raloxifene at 1 μM decreased IKur by 57.3 ± 3.3% (at + 50 mV, n = 10, P < 0.01 vs control). However, β-estradiol inhibited Ito1 (IC50 = 10.3 μM) without affecting IKur. The inhibitory effects of raloxifene and β-estradiol on Ito1 and/or IKur were unaffected by the estrogen receptor antagonist ICI 182,780. Our results indicate that raloxifene directly inhibits the human atrial repolarization potassium currents Ito1 and IKur. Whether raloxifene is beneficial for supraventricular arrhythmias remains to be studied. © 2007 Elsevier B.V. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/76870
ISSN
2015 Impact Factor: 2.73
2015 SCImago Journal Rankings: 1.115
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLiu, Hen_HK
dc.contributor.authorJin, MWen_HK
dc.contributor.authorXiang, JZen_HK
dc.contributor.authorHuang, Yen_HK
dc.contributor.authorSun, HYen_HK
dc.contributor.authorChiu, SWen_HK
dc.contributor.authorLau, CPen_HK
dc.contributor.authorLi, GRen_HK
dc.date.accessioned2010-09-06T07:25:48Z-
dc.date.available2010-09-06T07:25:48Z-
dc.date.issued2007en_HK
dc.identifier.citationEuropean Journal Of Pharmacology, 2007, v. 563 n. 1-3, p. 61-68en_HK
dc.identifier.issn0014-2999en_HK
dc.identifier.urihttp://hdl.handle.net/10722/76870-
dc.description.abstractThe selective estrogen receptor modulator raloxifene is widely used in the treatment of postmenopausal osteoporosis, and has cardioprotective properties. However, effects of raloxifene on cardiac ion channels are unclear. The present study was designed to investigate the effects of raloxifene and β-estradiol on transient outward and ultra-rapid delayed rectifier potassium currents (Ito1 and IKur) in human atrial myocytes with a whole cell patch-clamp technique. Ito1 was inhibited by raloxifene in a concentration-dependent manner with an IC50 of 0.9 μM. Raloxifene at 1 μM decreased Ito1 by 40.2 ± 1.9% (at + 50 mV, n = 14, P < 0.01 vs control). Time-dependent recovery from inactivation was slowed, and time to peak and time-dependent inactivation of Ito1 were significantly accelerated, while steady-state voltage dependent activation and inactivation of Ito1 were not affected by raloxifene. In addition, raloxifene remarkably suppressed IKur (IC50 = 0.7 μM). Raloxifene at 1 μM decreased IKur by 57.3 ± 3.3% (at + 50 mV, n = 10, P < 0.01 vs control). However, β-estradiol inhibited Ito1 (IC50 = 10.3 μM) without affecting IKur. The inhibitory effects of raloxifene and β-estradiol on Ito1 and/or IKur were unaffected by the estrogen receptor antagonist ICI 182,780. Our results indicate that raloxifene directly inhibits the human atrial repolarization potassium currents Ito1 and IKur. Whether raloxifene is beneficial for supraventricular arrhythmias remains to be studied. © 2007 Elsevier B.V. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ejpharen_HK
dc.relation.ispartofEuropean Journal of Pharmacologyen_HK
dc.rightsEuropean Journal of Pharmacology. Copyright © Elsevier BV.en_HK
dc.subject.meshAction Potentials - drug effectsen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshDelayed Rectifier Potassium Channels - antagonists & inhibitors - metabolismen_HK
dc.subject.meshDose-Response Relationship, Drugen_HK
dc.subject.meshEstradiol - analogs & derivatives - metabolism - pharmacologyen_HK
dc.subject.meshEstrogen Antagonists - pharmacologyen_HK
dc.subject.meshHeart Atria - cytology - drug effects - metabolismen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshMyocytes, Cardiac - drug effects - metabolismen_HK
dc.subject.meshPatch-Clamp Techniquesen_HK
dc.subject.meshPotassium - metabolismen_HK
dc.subject.meshPotassium Channel Blockers - pharmacologyen_HK
dc.subject.meshPotassium Channels - drug effects - metabolismen_HK
dc.subject.meshRaloxifene - pharmacologyen_HK
dc.subject.meshSelective Estrogen Receptor Modulators - pharmacologyen_HK
dc.subject.meshTime Factorsen_HK
dc.titleRaloxifene inhibits transient outward and ultra-rapid delayed rectifier potassium currents in human atrial myocytesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0014-2999&volume=563&issue=1-3&spage=61&epage=8&date=2007&atitle=Raloxifene+inhibits+transient+outward+and+ultra-rapid+delayed+rectifier+potassium+currents+in+human+atrial+myocytesen_HK
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.ejphar.2007.01.072en_HK
dc.identifier.pmid17337266-
dc.identifier.scopuseid_2-s2.0-34247113320en_HK
dc.identifier.hkuros126520en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34247113320&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume563en_HK
dc.identifier.issue1-3en_HK
dc.identifier.spage61en_HK
dc.identifier.epage68en_HK
dc.identifier.isiWOS:000246608300005-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridLiu, H=27171679500en_HK
dc.identifier.scopusauthoridJin, MW=35932258500en_HK
dc.identifier.scopusauthoridXiang, JZ=10641709700en_HK
dc.identifier.scopusauthoridHuang, Y=34770945300en_HK
dc.identifier.scopusauthoridSun, HY=35723049200en_HK
dc.identifier.scopusauthoridChiu, SW=37044597700en_HK
dc.identifier.scopusauthoridLau, CP=7401968501en_HK
dc.identifier.scopusauthoridLi, GR=7408462932en_HK

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