Stochastic spontaneous calcium release events and sodium channelopathies promote ventricular arrhythmias

Chaos. 2017 Sep;27(9):093910. doi: 10.1063/1.4999612.


Premature ventricular complexes (PVCs), the first initiating beats of a variety of cardiac arrhythmias, have been associated with spontaneous calcium release (SCR) events at the cell level. However, the mechanisms underlying the degeneration of such PVCs into arrhythmias are not fully understood. The objective of this study was to investigate the conditions under which SCR-mediated PVCs can lead to ventricular arrhythmias. In particular, we sought to determine whether sodium (Na+) current loss-of-function in the structurally normal ventricles provides a substrate for unidirectional conduction block and reentry initiated by SCR-mediated PVCs. To achieve this goal, a stochastic model of SCR was incorporated into an anatomically accurate compute model of the rabbit ventricles with the His-Purkinje system (HPS). Simulations with reduced Na+ current due to a negative-shift in the steady-state channel inactivation showed that SCR-mediated delayed afterdepolarizations led to PVC formation in the HPS, where the electrotonic load was lower, conduction block, and reentry in the 3D myocardium. Moreover, arrhythmia initiation was only possible when intrinsic electrophysiological heterogeneity in action potential within the ventricles was present. In conclusion, while benign in healthy individuals SCR-mediated PVCs can lead to life-threatening ventricular arrhythmias when combined with Na+ channelopathies.

MeSH terms

  • Action Potentials
  • Animals
  • Arrhythmias, Cardiac / pathology*
  • Arrhythmias, Cardiac / physiopathology
  • Calcium / metabolism*
  • Channelopathies / pathology*
  • Computer Simulation
  • Heart Conduction System / pathology
  • Heart Conduction System / physiopathology
  • Heart Ventricles / pathology*
  • Heart Ventricles / physiopathology
  • Models, Cardiovascular
  • Myocytes, Cardiac / metabolism
  • Purkinje Fibers / pathology
  • Purkinje Fibers / physiopathology
  • Rabbits
  • Sodium / metabolism*
  • Stochastic Processes
  • Ventricular Premature Complexes / pathology
  • Ventricular Premature Complexes / physiopathology


  • Sodium
  • Calcium