| Upregulation of ventricular potassium channels by chronic tamoxifen treatment. | |
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MedLine Citation:
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PMID: 21131637 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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AIMS: Tamoxifen is a selective oestrogen receptor modulator widely used in the prevention and treatment of breast cancer. Women receiving long-term tamoxifen therapy do not experience cardiac arrhythmias although acute perfusion of tamoxifen has been shown to inhibit cardiac K(+) currents. This observation suggests that chronic tamoxifen treatment does not negatively modulate cardiac K(+) currents. Therefore, we investigated the chronic effects of tamoxifen on K(+) currents and channels in mouse and guinea pig ventricles. METHODS AND RESULTS: Female mice and guinea pigs were treated with placebo or tamoxifen pellets for 60 days. Voltage-clamp experiments showed that the density of the Ca(2+)-independent transient outward (I(to)), the ultrarapid delayed rectifier (I(Kur)), the steady-state (I(ss)), and the inward rectifier (I(K1)) K(+) currents were increased in tamoxifen-treated mice ventricle. Western blot analysis revealed that protein expression of the underlying K(+) channels Kv4.3 (I(to)), Kv1.5 (I(Kur)), Kv2.1 (I(ss)), and Kir2.1 (I(K1)) were significantly higher in the ventricle of tamoxifen-treated mice. Protein expression of the K(+) channel subunits encoding I(Kr) and I(Ks) (ERG1, KCNQ1, and KCNE1) was also increased in tamoxifen-treated guinea pig ventricle. CONCLUSION: Conditions with high oestrogen levels are associated with reduced K(+) currents. Thus, conceivably, tamoxifen might prevent the inhibitory effects of oestrogen on K(+) channels by blocking the oestrogen receptors, which would explain the reported increase in K(+) currents. These findings could contribute to explain the absence of cardiac arrhythmia with long-term tamoxifen therapy. |
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Authors:
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Gracia El Gebeily; Céline Fiset |
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Publication Detail:
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Type: Journal Article Date: 2010-12-03 |
Journal Detail:
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Title: Cardiovascular research Volume: 90 ISSN: 1755-3245 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-03-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: England |
Other Details:
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Languages: eng Pagination: 68-76 Citation Subset: IM |
Affiliation:
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Research Center, Montreal Heart Institute, 5000 Bélanger, Montréal, Québec, Canada H1T 1C8. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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