Inhibitory effect of aloperine on transient outward potassium currents in rat cardiac myocytes

Objective: Aloperine (ALO) is an effective quinolizidine alkaloid. Previous research has demonstrated its antiarrhythmic effect by inhibiting voltage-gated sodium currents in rat ventricular myocytes. This study explored its effect on transient outward potassium currents (I to ) in rat atrial myocytes to identify potential targets in the context of ion channel currents. Methods: The I to characteristics in rat atrial myocytes were recorded using a whole-cell patch-clamp technique. Molecular docking was performed to validate ligand-protein binding interactions. Results: ALO at concentrations of 3 and 10 μM significantly reduced I to current densities. Gating kinetics analysis revealed ALO’s ability to slow I to activation, hasten inactivation, and prolong transition from inactive to resting state. Molecular docking revealed that ALO could stably bind to KCND2 . Conclusion: ALO may inhibit I to by slowing the activation process, accelerating inactivation, and delaying the recovery time after inactivation, potentially preventing acetylcholine-induced AF.