Ionic mechanisms of triggered activity in atrial cell models

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 β-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 β-adrenergic stimulation and stopped by ranolazine, a blocker of I_NaL. 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.