Class III antiarrhythmic drugs amiodarone and dronedarone impair KIR 2.1 backward trafficking
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F17%3A10362846" target="_blank" >RIV/00216208:11140/17:10362846 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1111/jcmm.13172" target="_blank" >http://dx.doi.org/10.1111/jcmm.13172</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1111/jcmm.13172" target="_blank" >10.1111/jcmm.13172</a>
Alternative languages
Result language
angličtina
Original language name
Class III antiarrhythmic drugs amiodarone and dronedarone impair KIR 2.1 backward trafficking
Original language description
Drug-induced ion channel trafficking disturbance can cause cardiac arrhythmias. The subcellular level at which drugs interfere in trafficking pathways is largely unknown. K(IR)2.1 inward rectifier channels, largely responsible for the cardiac inward rectifier current (I-K1), are degraded in lysosomes. Amiodarone and dronedarone are class III antiarrhythmics. Chronic use of amiodarone, and to a lesser extent dronedarone, causes serious adverse effects to several organs and tissue types, including the heart. Both drugs have been described to interfere in the late-endosome/lysosome system. Here we defined the potential interference in K(IR)2.1 backward trafficking by amiodarone and dronedarone. Both drugs inhibited I-K1 in isolated rabbit ventricular cardiomyocytes at supraclinical doses only. In HK-KWGF cells, both drugs dose- and time-dependently increased K(IR)2.1 expression (2.0 +/- 0.2-fold with amiodarone: 10 mu M, 24hrs; 2.3 +/- 0.3-fold with dronedarone: 5 mu M, 24hrs) and late-endosomal/lysosomal K(IR)2.1 accumulation. Increased K(IR)2.1 expression level was also observed in the presence of Na(v)1.5 co-expression. Augmented K(IR)2.1 protein levels and intracellular accumulation were also observed in COS-7, END-2, MES-1 and EPI-7 cells. Both drugs had no effect on K(v)11.1 ion channel protein expression levels. Finally, amiodarone (73.3 +/- 10.3% P<0.05 at -120mV, 5 mu M) enhanced I-KIR2.1 upon 24-hrs treatment, whereas dronedarone tended to increase I-KIR2.1 and it did not reach significance (43.8 +/- 5.5%, P=0.26 at -120mV; 2 mu M). We conclude that chronic amiodarone, and potentially also dronedarone, treatment can result in enhanced I-K1 by inhibiting K(IR)2.1 degradation.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30105 - Physiology (including cytology)
Result continuities
Project
<a href="/en/project/EE2.3.30.0061" target="_blank" >EE2.3.30.0061: Increasing of the R&D capacity at Charles University through new positions for graduates of doctoral studies</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Cellular and Molecular Medicine [online]
ISSN
1582-4934
e-ISSN
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Volume of the periodical
21
Issue of the periodical within the volume
10
Country of publishing house
DE - GERMANY
Number of pages
10
Pages from-to
2514-2523
UT code for WoS article
000411875400024
EID of the result in the Scopus database
2-s2.0-85018657730