The melanin synthesis enzyme dopachrome tautomerase (Dct) regulates intracellular Ca2+ in melanocytes. Homozygous Dct knockout (Dct−/−) adult mice are vulnerable to atrial arrhythmias (AA).The purpose of this study was to determine whether apamin-sensitive small conductance Ca2+-activated K+ (SK) currents are upregulated in Dct−/− mice and contribute to AA.Optical mapping was used to study the membrane potential of the right atrium in Langendorff perfused Dct−/− (n = 9) and Dct+/− (n = 9) mice.Apamin prolonged action potential duration (APD) by 18.8 ms (95% confidence interval [CI] 13.4–24.1 ms) in Dct−/− mice and by 11.5 ms (95% CI 5.4–17.6 ms) in Dct+/− mice at a pacing cycle length of 150 ms (P = .047). The pacing cycle length threshold to induce APD alternans was 48 ms (95% CI 34–62 ms) for Dct−/− mice and 21 ms (95% CI 12–29 ms) for Dct+/− mice (P = .002) at baseline, and it was 35 ms (95% CI 21–49 ms) for Dct−/− mice and 22 ms (95% CI 11–32 ms) for Dct+/− mice (P = .025) after apamin administration. Apamin prolonged post-burst pacing APD by 8.9 ms (95% CI 3.9–14.0 ms) in Dct−/− mice and by 1.5 ms (95% CI 0.7–2.3 ms) in Dct+/− mice (P = .005). Immunoblot and quantitative polymerase chain reaction analyses showed that protein and transcripts levels of SK1 and SK3 were increased in the right atrium of Dct−/− mice. AA inducibility (89% vs 11%; P = .003) and duration (281 seconds vs 66 seconds; P = .008) were greater in Dct−/− mice than in Dct+/− mice at baseline, but not different (22% vs 11%; P = 1.00) after apamin administration. Five of 8 (63%) induced atrial fibrillation episodes in Dct−/− mice had focal drivers.Apamin-sensitive SK current upregulation in Dct−/− mice plays an important role in the mechanism of AA.