title: Effects of Ticagrelor on Ionic Currents and Contractility in Rat Ventricular Myocytes.
abstract: OBJECTIVE
  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 Ca(2+) 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.
authors.affiliation: Faculty of Medicine Department of Cardiology, Akdeniz University, Antalya, Turkey.
authors.forename: Murathan
authors.initials: M
authors.lastname: Kucuk
authors.affiliation: Faculty of Medicine Department of Biophysics, Akdeniz University, Antalya, Turkey.
authors.forename: Murat C
authors.initials: MC
authors.lastname: Celen
authors.affiliation: Faculty of Medicine Department of Biophysics, Akdeniz University, Antalya, Turkey.
authors.forename: Bilge E
authors.initials: BE
authors.lastname: Yamasan
authors.affiliation: Faculty of Medicine Department of Biophysics, Akdeniz University, Antalya, Turkey.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Olgar
authors.affiliation: Faculty of Medicine Department of Biophysics, Akdeniz University, Antalya, Turkey. osemir@akdeniz.edu.tr.
authors.forename: Semir
authors.initials: S
authors.lastname: Ozdemir
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D004553:Electric Conductivity; D004558:Electric Stimulation; D006352:Heart Ventricles / Q000166:cytology*; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D012518:Sarcomeres / Q000187:drug effects; D000077486:Ticagrelor
chemical_list: D020746:Calcium Channels, L-Type; D015221:Potassium Channels; D000077486:Ticagrelor; D000241:Adenosine
keywords: Action potential; Contractility; L-type Ca2+ currents; Ticagrelor; Ventricular myocytes