Activated human platelet products induce proarrhythmic effects in ventricular myocytes

J.S.S.G. de Jong, A.O. Verkerk, M.M.G.J. van Borren, O.M. Zakhrabova-Zwiauer, R. Nieuwland, J.C.M. Meijers, J.W.N. Akkerman, A.A.M. Wilde, H.L. Tan, L.R.C. Dekker

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Abstract

Sudden cardiac death remains one of the most prevalent modes of death and is mainly caused by ventricular fibrillation (VF) in the setting of acute ischemia resulting from coronary thrombi. Animal experiments have shown that platelet activation may increase susceptibility of ischemic myocardium to VF, but the mechanism is unknown. In the present study, we evaluated the effects of activated blood platelet products (ABPPs) on electrophysiological properties and intracellular Ca(2+) (Ca(2+)(i)) homeostasis. Platelets were collected from healthy volunteers. After activation, their secreted ABPPs were added to superfusion solutions. Rabbit ventricular myocytes were freshly isolated, and membrane potentials and Ca(2+)(i) were recorded using patch-clamp methodology and indo-1 fluorescence measurements, respectively. ABPPs prolonged action potential duration and induced early and delayed afterdepolarizations. ABPPs increased L-type Ca(2+) current (I(Ca,L)) density, but left densities of sodium current, inward rectifier K(+) current, transient outward K(+) current, and rapid component of the delayed rectifier K(+) current unchanged. ABPPs did not affect kinetics or (in)activation properties of membrane currents. ABPPs increased systolic Ca(2+)(i), Ca(2+)(i) transient amplitude, and sarcoplasmic reticulum Ca(2+) content. ABPPs did not affect the Na(+)-Ca(2+) exchange current (I(NCX)) in Ca(2+)-buffered conditions. Products secreted from activated human platelets induce changes in I(Ca,L) and Ca(2+)(i), which result in action potential prolongation and the occurrence of early and delayed afterdepolarizations in rabbit myocytes. These changes may trigger and support reentrant arrhythmias in ischemia models of coronary thrombosis.

Original languageEnglish
Pages (from-to)347-56
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume51
Issue number3
DOIs
Publication statusPublished - Sep 2011
Externally publishedYes

Keywords

  • Action Potentials
  • Animals
  • Biological Factors
  • Blood Platelets
  • Calcium
  • Calcium Channels
  • Heart Ventricles
  • Homeostasis
  • Humans
  • Myocytes, Cardiac
  • Platelet Activation
  • Rabbits
  • Sarcoplasmic Reticulum
  • Trypsin
  • Ventricular Function

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  • Cite this

    de Jong, J. S. S. G., Verkerk, A. O., van Borren, M. M. G. J., Zakhrabova-Zwiauer, O. M., Nieuwland, R., Meijers, J. C. M., Akkerman, J. W. N., Wilde, A. A. M., Tan, H. L., & Dekker, L. R. C. (2011). Activated human platelet products induce proarrhythmic effects in ventricular myocytes. Journal of Molecular and Cellular Cardiology, 51(3), 347-56. https://doi.org/10.1016/j.yjmcc.2011.05.016