File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Effects of the antifungal antibiotic clotrimazole on human cardiac repolarization potassium currents

TitleEffects of the antifungal antibiotic clotrimazole on human cardiac repolarization potassium currents
Authors
KeywordsClotrimazole
hERG channel
Human cardiac repolarization K + currents
Recombinant human cardiac KCNQ1/KCNE1
Transient outward K + current
Ultra-rapidly delayed rectifier K + current
Issue Date2006
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1
Citation
British Journal Of Pharmacology, 2006, v. 147 n. 3, p. 289-297 How to Cite?
Abstract1. The antifungal antibiotic clotrimazole (CLT) shows therapeutic effects on cancer, sickle cell disease, malaria, etc. by inhibiting membrane intermediate-conductance Ca 2+-activated K + channels (IK Ca). However, it is unclear whether this drug would affect human cardiac K + currents. The present study was therefore designed to investigate the effects of CLT on transient outward K + current (I tol), and ultra-rapid delayed rectifier K + current (I Kur) in isolated human atrial myocytes, and cloned hERG channel current (I hERG) and recombinant human cardiac KCNQ1/KCNE1 channel current (I Ks) expressed in HEK 293 cells. 2. It was found that CLT inhibited I tol with an IC 50 of 29.5 μM, accelerated I tol inactivation, and decreased recovery of I tol from inactivation. In addition, CLT inhibited human atrial I Kur in a concentration-dependent manner (IC 50 = 7.6 μM). 3. CLT substantially suppressed I hERG (IC 50 = 3.6 μM), and negatively shifted the activation conductance of IhERG- Moreover, CLT inhibited I Ks (IC 50= 15.1 μM), and positively shifted the activation conductance of the current. 4. These results indicate that the antifungal antibiotic CLT substantially inhibits human cardiac repolarization K + currents including I tol, I Kur, I hERG, and I Ks. However, caution is recommended when correlating the observed in vitro effects on cardiac ion currents to the clinical relevance. © 2006 Nature Publishing Group All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/49051
ISSN
2015 Impact Factor: 5.259
2015 SCImago Journal Rankings: 2.368
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTian, Men_HK
dc.contributor.authorDong, MQen_HK
dc.contributor.authorChiu, SWen_HK
dc.contributor.authorLau, CPen_HK
dc.contributor.authorLi, GRen_HK
dc.date.accessioned2008-06-12T06:33:21Z-
dc.date.available2008-06-12T06:33:21Z-
dc.date.issued2006en_HK
dc.identifier.citationBritish Journal Of Pharmacology, 2006, v. 147 n. 3, p. 289-297en_HK
dc.identifier.issn0007-1188en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49051-
dc.description.abstract1. The antifungal antibiotic clotrimazole (CLT) shows therapeutic effects on cancer, sickle cell disease, malaria, etc. by inhibiting membrane intermediate-conductance Ca 2+-activated K + channels (IK Ca). However, it is unclear whether this drug would affect human cardiac K + currents. The present study was therefore designed to investigate the effects of CLT on transient outward K + current (I tol), and ultra-rapid delayed rectifier K + current (I Kur) in isolated human atrial myocytes, and cloned hERG channel current (I hERG) and recombinant human cardiac KCNQ1/KCNE1 channel current (I Ks) expressed in HEK 293 cells. 2. It was found that CLT inhibited I tol with an IC 50 of 29.5 μM, accelerated I tol inactivation, and decreased recovery of I tol from inactivation. In addition, CLT inhibited human atrial I Kur in a concentration-dependent manner (IC 50 = 7.6 μM). 3. CLT substantially suppressed I hERG (IC 50 = 3.6 μM), and negatively shifted the activation conductance of IhERG- Moreover, CLT inhibited I Ks (IC 50= 15.1 μM), and positively shifted the activation conductance of the current. 4. These results indicate that the antifungal antibiotic CLT substantially inhibits human cardiac repolarization K + currents including I tol, I Kur, I hERG, and I Ks. However, caution is recommended when correlating the observed in vitro effects on cardiac ion currents to the clinical relevance. © 2006 Nature Publishing Group All rights reserved.en_HK
dc.format.extent388 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1en_HK
dc.relation.ispartofBritish Journal of Pharmacologyen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectClotrimazoleen_HK
dc.subjecthERG channelen_HK
dc.subjectHuman cardiac repolarization K + currentsen_HK
dc.subjectRecombinant human cardiac KCNQ1/KCNE1en_HK
dc.subjectTransient outward K + currenten_HK
dc.subjectUltra-rapidly delayed rectifier K + currenten_HK
dc.titleEffects of the antifungal antibiotic clotrimazole on human cardiac repolarization potassium currentsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0007-1188&volume=147&issue=3&spage=289&epage=297&date=2006&atitle=Effects+of+the+antifungal+antibiotic+clotrimazole+on+human+cardiac+repolarization+potassium+currentsen_HK
dc.identifier.emailLi, GR:grli@hkucc.hku.hken_HK
dc.identifier.authorityLi, GR=rp00476en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1038/sj.bjp.0706590en_HK
dc.identifier.pmid16341233-
dc.identifier.pmcidPMC1751304en_HK
dc.identifier.scopuseid_2-s2.0-32244447329en_HK
dc.identifier.hkuros112633-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-32244447329&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume147en_HK
dc.identifier.issue3en_HK
dc.identifier.spage289en_HK
dc.identifier.epage297en_HK
dc.identifier.isiWOS:000235152100008-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridTian, M=49764253600en_HK
dc.identifier.scopusauthoridDong, MQ=7202127303en_HK
dc.identifier.scopusauthoridChiu, SW=37044597700en_HK
dc.identifier.scopusauthoridLau, CP=7401968501en_HK
dc.identifier.scopusauthoridLi, GR=7408462932en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats