Transient outward K+ current inhibition suppresses early afterdepolarizations and ventricular arrhythmias via trajectory displacement away from an oscillatory regime

Excitable biological systems can undergo abrupt transitions from stable rhythmic activity to pathological oscillations through subtle changes in slow-fast dynamical structure. In cardiac ventricular myocytes, such transitions manifest as early afterdepolarizations (EADs), which are closely associated with triggered activity and polymorphic ventricular tachycardia. Although the transient outward K+ current (Ito) shapes early repolarization, its dynamical role in EAD-mediated instability remains incompletely understood. We investigated how Ito suppression modifies excitation dynamics using two-dimensional ventricular tissue simulations combined with bifurcation and slow-fast analyses in a human ventricular myocyte model exhibiting EADs. Reduction of Ito markedly suppressed triggered activity and ventricular tachycardia-like dynamics in a manner dependent on both the magnitude and timing of inhibition. Single-cell bifurcation analysis revealed progressive destabilization of EAD-associated oscillations with decreasing Ito. Slow-fast decomposition further demonstrated that Ito suppression does not eliminate the underlying oscillatory structure of the fast subsystem but instead shifts the plateau potential in a depolarizing direction, thereby displacing system trajectories away from the oscillatory regime responsible for EAD generation. As a result, trajectories bypass the oscillatory attractor and repolarize directly toward the stable resting equilibrium. These findings show that Ito inhibition suppresses pathological oscillations not by structural destruction of the oscillatory bifurcation framework but by modifying trajectory accessibility within it. This work provides a multiscale dynamical systems interpretation of EAD suppression and identifies Ito as a key control parameter governing ventricular electrical stability.