Atrial fibrillation (AF) is the most common sustained arrhythmia and contributes to cardiac morbidity and mortality. Extension of the atrial effective refractory period through block of potassium channels is a therapeutic strategy for AF, with an atrial-selective drug being desired to avoid potentially lethal ventricular arrhythmias. Small-conductance calcium-activated potassium (SK) channels have been recently suggested as a promising atrial selective target, but disagreement exists concerning expression and function of these channels in atrial myocytes. Visualization of antibody labelling using confocal microscopy showed the presence of SK2 protein in mouse atrial myocytes with localization of staining along the z-lines. Whole-cell recordings revealed outward currents positive to −20 mV that were sensitive to two SK inhibitors, apamin and UCL1684. Current was blocked by apamin with an IC50 of 118 pM, close to reported values for homomeric SK2 current in mammalian cell lines. Action potential duration (APD) was prolonged more by application of UCL1684 than apamin, at a firing frequency of 0.2 Hz. The effect of UCL1684 was greater with a firing frequency of 2 Hz, producing a decrease of the stability of APD and increasing beat-to-beat variability (BVR) in APD. These data suggest that functional SK channels are present in the mouse atrium. However, the effects of apamin were different under voltage- or current-clamp conditions, while the effects of UCL1684 were similar. This difference might arise from atrial myocytes expressing more than one population of SK channels, with one being apamin-insensitive and contributing to action potential repolarization. The effect of UCL1684 on APD is consistent with the recruitment of more SK channel activity at higher firing frequencies. Block of these SK channels increases BVR, a marker of drug induced repolarization-related proarrhythmias, raising the possibility that SK inhibition could be proarrhythmic.