All

What are you looking for?

All
Projects
Results
Organizations

Quick search

  • Projects supported by TA ČR
  • Excellent projects
  • Projects with the highest public support
  • Current projects

Smart search

  • That is how I find a specific +word
  • That is how I leave the -word out of the results
  • “That is how I can find the whole phrase”

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&lt;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

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • 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

  • 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