The results of this study indicate that the PKC/ERK signaling pathway is involved in the downregulation of SK2 and the upregulation of SK3 in the atrium of T2DM rats and long-term metformin treatment prevents the SK2 downregulation and the SK3 upregulation through inhibiting the PKC/ERK signaling pathway. Here, KCNN2 is linked to type 2 diabetes mellitus.