In this paper, we report on the comprehensive alcohol-/ion-responsive properties of a smart copolymer poly（N- isopropylacry]amide-co-benzo-18-crown-6-acrylamide） （P（NIPAM-co-BCAm））. The orthogonal design method is adopted for experimental design. The experimental results show that alcohol can trigger the shrinking and Ba2t can induce the swelling of the P（NIPAM-co-BCAm） copolymer. According to the phase transition tempera- ture （LCST） change results of the copolymer, the influence of variables on the LCST changes weakens in the following order： alcohol concentration 〉 alcohol species 〉 metal ion species 〉 BCAm concentration 〉 ion concentration. The larger the alcohol concentration and the larger the molecular size of alcohols, the lower the LCST value; on the contrary, the more the BCAm content in the copolymer or the larger the BCAm/ion complex stability constant （IgK） or the larger the ion concentration is, the higher the LCST value. For a P（NIPAM-co-BCAm ） copolymer with a fixed BCAm content, a binary function of ion concentration and IgK of BCAm/ion is developed to precisely predict the LCST values of the copolymer in different metal ion solutions. The results provide valuable information for fabricating artificial biomimetic G-protein-gated inwardly rectifying potassium （GIRK） channels that are activated by alcohol and inhibited by Ba2＋.
