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AIM: To investigate the effects of exogenous unsaturated fatty acids on calcium-activated potassium current [Ik(Ca)]in gastric antral circular myocytes of guinea pigs.METHODS: Gastric myocytes were isolated by collagenase from the antral circular layer of guinea pig stomach. The whole-cell patch clamp technique was used to record Ik(Ca)in the isolated single smooth muscle cells with or without different concentrations of arachidonic acid (AA), linoleic acid (LA), and oleic acid (OA).RESULTS: AA at concentrations of 2,5 and 10 μmol/L markedly increased IK(ca)in a dose-dependent manner. LA at concentrations of 5, 10 and 20 μmol/L also enhanced IK(Ca)in a dose-dependent manner. The increasing potency of AA, LA, and oleic acid (OA) on Ik(Ca) at the same concentration(10 μmol/L) was in the order of AA＞LA＞OA. AA (10 μmol/L)-induced increase of Ik(Ca) was not blocked by H-7 (10 μmol/L), an inhibitor of protein kinase C (PKC), or indomethacin (10 μmol/L),an inhibitor of the cyclooxygenase pathway, and 17-octadecynoic acid (10 μmol/L), an inhibitor of the cytochrome P450 pathway, but weakened by nordihydroguaiaretic acid(10 μmol/L), an inhibitor of the lipoxygenase pathway.CONCLUSION: Unsaturated fatty acids markedly increase Ik(Ca), and the enhancing potencies are related to the number of double bonds in the fatty acid chain. The lipoxygenase pathway of unsaturated fatty acid metabolism is involved in the unsaturated fatty acid-induced increase of IK(Ca) in gastric antral circular myocytes of guinea pigs.