Oleic Acid Inhibits the KATP Channel Subunit Kir6.1 and the KATP Current in Human Umbilical Artery Smooth Muscle Cells

Background:The objective of the present study was to determine the effect of various concentrations of oleic acid (OA) on K-ATP channel expression and the potential relationship to exogenous nitrogen monoxide and protein kinase C levels.Methods:Human umbilical artery smooth muscle cells (HUASMCs), between the 7th and 10th passages, were divided into control group, OA group (final OA concentration of 0, 50, 100 or 200 mol/L), nitric oxide (NO) intervention group, protein kinase C inhibitor group or GF-109203X (GFX) intervention group. Western immunoblotting was used to detect the protein expression of the K-ATP channel subunit Kir6.1. Also, quantitative real-time polymerase chain reaction analysis to determine Kir6.1 messenger RNA levels and whole-cell patch clamping to measure K-ATP currents were performed.Results:The results suggested that OA inhibited Kir6.1 protein and messenger RNA expression in HUASMCs. Under a high concentration of potassium (140 mmol/L), 100 mol/L OA significantly reduced ATP-sensitive potassium current density, whereas a low extracellular concentration of potassium (5.4 mmol/L) did not influence K-ATP density. Pretreatment with either exogenous NO or GFX weakened the OA-induced inhibition of K-ATP in HUASMCs.Conclusions:The study demonstrated that OA inhibited Kir6.1, a K-ATP channel subunit, in HUASMCs, and indirectly inhibited the K-ATP current. In addition, the results indicated that NO and/or GFX partially reversed OA inhibition in HUASMCs.