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Effects of Ticagrelor on Ionic Currents and Contractility in Rat Ventricular Myocytes

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Abstract

Purpose

Antiplatelet therapy has been widely used for management of patients with ischaemic heart diseases or thrombotic events. Experimental studies have shown that ticlopidine and clopidogrel decreased L-type Ca2+ currents (ICaL), altered action potential (AP) duration and thence exerted negative inotropic effects. In this study we tested if ticagrelor, a non-thienopyridine agent, has any influence on contractile and electrical properties of isolated ventricular myocytes.

Methods

Cardiomyocytes were isolated from male rat hearts with an enzymatic dissociation procedure and left ventricular myocytes were used for experiments. The effects of ticagrelor (1 μM) on sarcomere shortening, ionic currents and action potentials were measured at 36 ± 1 °C.

Results

Ticagrelor significantly reduced ICaL density (~18 %, p < 0.01) of ventricular myocytes and this effect was reversible. In consistence, it also decreased sarcomere shortening of electrically stimulated cardiomyocytes (13 %, p < 0.05), while it did not change relaxation rates. Repolarizing K+ currents and AP duration were unaffected by 1 μM ticagrelor application.

Conclusions

Ticagrelor exerts a significant influence on contractile properties and membrane currents of ventricular myocytes similarly to thienopyridine agents. The impact of ticagrelor on cardiac excitation-contraction coupling elements is important, since it is widely used for the treatment of patients with heart diseases.

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Acknowledgments

This work was supported by Akdeniz University Research Coordination Unit.

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Authors and Affiliations

  1. Faculty of Medicine Department of Cardiology, Akdeniz University, Antalya, Turkey

    Murathan Kucuk

  2. Faculty of Medicine Department of Biophysics, Akdeniz University, Antalya, Turkey

    Murat C. Celen, Bilge E. Yamasan, Yusuf Olgar & Semir Ozdemir

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  1. Murathan Kucuk
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  2. Murat C. Celen
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  3. Bilge E. Yamasan
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  4. Yusuf Olgar
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  5. Semir Ozdemir
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Correspondence to Semir Ozdemir.

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Kucuk, M., Celen, M.C., Yamasan, B.E. et al. Effects of Ticagrelor on Ionic Currents and Contractility in Rat Ventricular Myocytes. Cardiovasc Drugs Ther 29, 419–424 (2015). https://doi.org/10.1007/s10557-015-6617-2

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