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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    48 activation of IKr
    49 agonist ropinirole
    50 amplitude
    51 applications
    52 block
    53 canine ventricular cardiomyocytes
    54 canine ventricular myocytes
    55 cardiac effects
    56 cardiomyocytes
    57 cases
    58 cellular cardiac effects
    59 changes
    60 characteristics
    61 clamp
    62 clamp conditions
    63 clamp technique
    64 clinical applications
    65 coefficient
    66 concentration
    67 concentration-dependent effects
    68 concentration-dependent inhibition
    69 conditions
    70 constants
    71 conventional patch clamp
    72 conventional whole-cell patch clamp
    73 current
    74 deactivation time constants
    75 depolarization
    76 depression
    77 dopamine receptor agonist ropinirole
    78 duration
    79 early repolarization
    80 effect
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    82 high concentrations
    83 information
    84 inhibition
    85 inhibition of IKr
    86 intoxication
    87 ion current
    88 little information
    89 long QT syndrome
    90 maximum rate
    91 microelectrodes
    92 morphology
    93 myocytes
    94 overdose
    95 patch clamp
    96 patients
    97 plateau
    98 positive voltage
    99 potential characteristics
    100 potential duration
    101 potential morphology
    102 potential voltage clamp conditions
    103 potential voltage clamp techniques
    104 present study
    105 proarrhythmic risk
    106 rate
    107 receptor agonist ropinirole
    108 rectifier
    109 repolarization
    110 results
    111 risk
    112 ropinirole
    113 ropinirole treatment
    114 significant changes
    115 slow deactivation time constants
    116 spite
    117 standard microelectrodes
    118 study
    119 suppression
    120 syndrome
    121 technique
    122 time constants
    123 treatment
    124 values
    125 ventricular cardiomyocytes
    126 ventricular myocytes
    127 voltage
    128 voltage-clamp conditions
    129 voltage-clamp technique
    130 washout
    131 whole-cell patch clamp
    132 widespread clinical application
    133 μM
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