Ontology type: schema:ScholarlyArticle
2010-07-29
AUTHORSJózsef Simkó, Norbert Szentandrássy, Gábor Harmati, László Bárándi, Balázs Horváth, János Magyar, Tamás Bányász, István Lőrincz, Péter P. Nánási
ABSTRACTIn spite of its widespread clinical application, there is little information on the cellular cardiac effects of the dopamine receptor agonist ropinirole. In the present study, therefore, the concentration-dependent effects of ropinirole on action potential morphology and the underlying ion currents were studied in enzymatically dispersed canine ventricular cardiomyocytes using standard microelectrode, conventional whole-cell patch clamp, and action potential voltage clamp techniques. At concentrations ≥ 1 μM, ropinirole increased action potential duration (APD90) and suppressed the rapid delayed rectifier K+ current (IKr) with an IC50 value of 2.7 ± 0.25 μM and Hill coefficient of 0.92 ± 0.09. The block increased with increasing depolarizations to more positive voltages, but paradoxically, the activation of IKr was accelerated by 3 μM ropinirole (time constant decreased from 34 ± 4 to 14 ± 1 ms). No significant changes in the fast and slow deactivation time constants were observed with ropinirole. At higher concentrations, ropinirole decreased the amplitude of early repolarization (at concentrations ≥ 10 μM), reduced the maximum rate of depolarization and caused depression of the plateau (at concentrations ≥ 30 μM), and shortened APD measured at 50% repolarization (at 300 μM) indicating a concentration-dependent inhibition of Ito, INa, and ICa. Suppression of IKr, Ito, and ICa has been confirmed under conventional patch clamp and action potential voltage clamp conditions. IKs and IK1 were not influenced significantly by ropinirole at concentrations less than 300 μM. All these effects of ropinirole were fully reversible upon washout. The results indicate that ropinirole treatment may carry proarrhythmic risk for patients with inherited or acquired long QT syndrome due to inhibition of IKr—especially in cases of accidental overdose or intoxication. More... »
PAGES213-220
http://scigraph.springernature.com/pub.10.1007/s00210-010-0538-1
DOIhttp://dx.doi.org/10.1007/s00210-010-0538-1
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PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/20668839
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