Complementary molecular, biophysical, and molecular methods were used and showed that (1) SK2 and SK3 channels are present in the porcine atria in both HC and in pigs with vernakalant-resistant AF, (2) AP14145 is a reasonably potent and selective inhibitor of the SK3 current, and (3) SK channel inhibition by AP14145 selectively prolongs the refractory period in porcine LA but not in the LV. Here, KCNN3 is linked to atrial fibrillation.