Absence of arrhythmogenic effects in cAMP subcellular compartments supports PDE8 as a target in atrial fibrillation

Background

Targeting Phosphodiesterase 8B (PDE8B) has been proposed as a strategy to restore L-type Ca2+ current (ICa,L) in patients with atrial fibrillation (AF). However, the effects of total PDE8 inhibition on other Ca2+ handling or 3',5'-cyclic adenosine monophosphate (cAMP) nanodomains have not been assessed and thus the potential proarrhythmic consequences are still undetermined.