Objective: This study investigates the functional relationship between PKA and SK2 channels in human AF.Methods and Results: In whole-cell patch-clamp experiments with isolated human atrial cardiomyocytes, the SK2 channel current densities(pA/pF)as well as the ration in the total inward currents were significantly increased in AF.Among these currents, PKA-selective inhibitor (H-89) reduced SK2 currents in the sinus rhythm (SR) and AF cardiomyocytes, with a greater degree of inhibition in AF.Morever, the ration of SK2 currents in the total inward currents can nearly be normalized to the SR levels after the application of H-89.Our data suggest that the increase of SK2 currents underlies the occurrence and maintenance ofAF.PKA-dependent regulation involves the remodeling of SK2 channels, which may be the important implications as a new therapeutic option for treatment of AF.