Dual effects of arachidonic acid on ATP-sensitive K+ current of coronary smooth muscle cells

ATP-sensitive K-channels (K-ATP) play a major role in controlling blood vessel tone, particularly in coronary vasculature. Arachidonic acid (AA) exhibits potent vasorelaxant effects on coronary arteries with unclear mechanisms. We examined the activity of AA on the K-ATP channel of dog coronary artery smooth muscle cells using the whole cell voltage-clamp technique. AA was found to have dual effects on the K-ATP current. In cells dialyzed with 1 mM ATP pipette solution, external application of AA activated the K-ATP current with a bell-shaped concentration-response curve. K-ATP current (-50 mV) increased from 1.0 +/- 1.1 to 4.6 +/- 3.0, 25 +/- 9, 43 +/- 13, 26 +/- 10, and 23 +/- 16 pA by 1, 2, 4, 8, and 16 mu M AA, respectively. If K-ATP current was activated by dialyzing the cell with ATP-free pipette solution, external application of AA (from 2 to 16 mu M) inhibited the K-ATP current (half-maximal inhibitory concentration = 3.8 mu M). Pretreatment of cells with 10 mu M indomethacin or 10 mu M nordihydroguaiaretic acid, which respectively blocked the cyclooxygenase or lipoxygenase pathway of AA metabolism, did not prevent the dual effects of AA. Eicosatetraynoic acid (ETYA), the nonmetabolizable analogue of AA, also produced dual effects on the K-ATP current. ETYA (4 mu M) increased the K-ATP current (-50 mV) from 2.9 +/- 1.2 to 37 +/- 7 pA in 1 mM intracellular ATP, whereas 8 mu M ETYA inhibited the K-ATP current in 0 mM intracellular ATP by 71 +/- 3%. These results suggest that the dual effects of AA on the K-ATP current of dog coronary smooth muscle cells do not require AA metabolism. Activation of K-ATP channels in smooth muscle cells may contribute to the AA-induced coronary vasodilation.