Effects of ropinirole on action potential characteristics and the underlying ion currents in canine ventricular myocytes View Full Text


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Article Info

DATE

2010-07-29

AUTHORS

József Simkó, Norbert Szentandrássy, Gábor Harmati, László Bárándi, Balázs Horváth, János Magyar, Tamás Bányász, István Lőrincz, Péter P. Nánási

ABSTRACT

In 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... »

PAGES

213-220

References to SciGraph publications

  • 1981-08. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches in PFLÜGERS ARCHIV - EUROPEAN JOURNAL OF PHYSIOLOGY
  • 2000-10. Clinical Pharmacokinetics of Ropinirole in CLINICAL PHARMACOKINETICS
  • 2006-04-04. Contribution of IKs to ventricular repolarization in canine myocytes in PFLÜGERS ARCHIV - EUROPEAN JOURNAL OF PHYSIOLOGY
  • 2005-06-11. Asymmetrical distribution of ion channels in canine and human left-ventricular wall: epicardium versus midmyocardium in PFLÜGERS ARCHIV - EUROPEAN JOURNAL OF PHYSIOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00210-010-0538-1

    DOI

    http://dx.doi.org/10.1007/s00210-010-0538-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1031160831

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20668839


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    96 potential characteristics
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    99 present study
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    103 repolarization
    104 results
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    106 ropinirole
    107 ropinirole treatment
    108 significant changes
    109 spite
    110 standard microelectrodes
    111 study
    112 suppression
    113 syndrome
    114 technique
    115 time constants
    116 treatment
    117 values
    118 ventricular cardiomyocytes
    119 ventricular myocytes
    120 voltage
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    122 voltage-clamp technique
    123 washout
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