Effects of tacrolimus on action potential configuration and transmembrane ion currents in canine ventricular cells View Full Text


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Article Info

DATE

2012-12-19

AUTHORS

László Szabó, Norbert Szentandrássy, Kornél Kistamás, Bence Hegyi, Ferenc Ruzsnavszky, Krisztina Váczi, Balázs Horváth, János Magyar, Tamás Bányász, Balázs Pál, Péter P. Nánási

ABSTRACT

Tacrolimus is a commonly used immunosuppressive agent which causes cardiovascular complications, e.g., hypertension and hypertrophic cardiomyopathy. In spite of it, there is little information on the cellular cardiac effects of the immunosuppressive agent tacrolimus in larger mammals. In the present study, therefore, the concentration-dependent effects of tacrolimus on action potential morphology and the underlying ion currents were studied in canine ventricular cardiomyocytes. Standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques were applied in myocytes enzymatically dispersed from canine ventricular myocardium. Tacrolimus (3–30 μM) caused a concentration-dependent reduction of maximum velocity of depolarization and repolarization, action potential amplitude, phase-1 repolarization, action potential duration, and plateau potential, while no significant change in the resting membrane potential was observed. Conventional voltage clamp experiments revealed that tacrolimus concentrations ≥3 μM blocked a variety of ion currents, including ICa, Ito, IK1, IKr, and IKs. Similar results were obtained under action potential voltage clamp conditions. These effects of tacrolimus developed rapidly and were fully reversible upon washout. The blockade of inward currents with the concomitant shortening of action potential duration in canine myocytes is the opposite of those observed previously with tacrolimus in small rodents. It is concluded that although tacrolimus blocks several ion channels at higher concentrations, there is no risk of direct interaction with cardiac ion channels when applying tacrolimus in therapeutic concentrations. More... »

PAGES

239-246

References to SciGraph publications

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  • 2000-01. Electrophysiological effects of fluoxetine in mammalian cardiac tissues in NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY
  • 2000-03. Electrophysiological effects of bimoclomol in canine ventricular myocytes in NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY
  • 2010-07-29. Effects of ropinirole on action potential characteristics and the underlying ion currents in canine ventricular myocytes in NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY
  • 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
  • 2001-04. Different effects of endothelin-1 on calcium and potassium currents in canine ventricular cells in NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY
  • 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
  • 2004-08-26. Effects of norfluoxetine on the action potential and transmembrane ion currents in canine ventricular cardiomyocytes in NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY
  • 2002-07-25. Electrophysiological effects of risperidone in mammalian cardiac cells in NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY
  • 2005-05. Risperidone-induced action potential prolongation is attenuated by increased repolarization reserve due to concomitant block of ICa,L in NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY
  • 2009-03-31. The effects of over-expression of the FK506-binding protein FKBP12.6 on K+ currents in adult rabbit ventricular myocytes in PFLÜGERS ARCHIV - EUROPEAN JOURNAL OF PHYSIOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00210-012-0823-2

    DOI

    http://dx.doi.org/10.1007/s00210-012-0823-2

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1025688667

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23250339


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