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. The gene discussed is KCNN3; the disease is type 2 diabetes mellitus.