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 or 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 microM 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 microM) inhibited the K(ATP) current (half-maximal inhibitory concentration = 3.8 microM). Pretreatment of cells with 10 microM indomethacin or 10 microM 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 microM) increased the K(ATP) current (-50 mV) from 2.9 +/- 1.2 to 37 +/- 7 pA in 1 mM intracellular ATP, whereas 8 microM 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.
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Upjohn Laboratories, Kalamazoo, Michigan 49007, USA.
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D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D003956:Dialysis; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D007213:Indomethacin / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000502:physiology*; D012996:Solutions
D012996:Solutions; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; D009637:Masoprocol; D000255:Adenosine Triphosphate; D011188:Potassium; D007213:Indomethacin