Key result
A 500% increase in late sodium current reduced the action potential excitation threshold by 30% and, when combined with decreased IK1 and increased ICaL, initiated spontaneous triggered activity.
Why the study?
Does increased late sodium current (INaL) combined with other pathological changes initiate triggered activity in atrial cell models?
Does increased late sodium current (INaL) combined with other pathological changes initiate triggered activity in atrial cell models?
Computational modeling demonstrates that pathologically increased late sodium current, combined with beta-adrenergic stimulation and reduced potassium currents, can initiate triggered activity in atrial cells, providing a potential mechanism for paroxysmal atrial fibrillation.
Spontaneous electrical activity in the atria, primarily near the pulmonary veins (PVs), is strongly linked with triggers for atrial fibrillation (AF). However, mechanisms of such triggered activity are incompletely understood. In this study, we use electrophysiologically detailed atrial cell models to investigate the role of late sodium current, INaL, in the mechanisms of triggered activity. The model simulations show that increases of this inward current (seen in several conditions that predispose to AF) can play a key role in the initiation of spontaneous diastolic depolarisation in atrial cells. Sustained triggered activity also requires contributions of other factors − increased L-type calcium current and decreased potassium currents − which are associated with -adrenergic stimulation of atrial cells. The proposed mechanism is in agreement with experiments showing that triggered activity can be induced in the PVs primarily by -adrenergic stimulation and stopped by ranolazine, a blocker of INaL. Triggered activity in the model can be halted in fibrotic conditions, when myocytes are coupled to fibroblasts. Hence, the mechanism may be more relevant to paroxysmal AF.
No takes yet. Share an insight, caveat, or question.
Varela et al. (2014) studied Atrial fibrillation. Increased late sodium current (INaL) and ionic remodeling vs. Control atrial cell model was evaluated on Action potential excitation threshold and spontaneous diastolic depolarizations. A 500% increase in late sodium current reduced the action potential excitation threshold by 30% and, when combined with decreased IK1 and increased ICaL, initiated spontaneous triggered activity.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: