AJP - Heart and Circulatory Physiology, Vol 270, Issue 6 1957-H1962, Copyright © 1996 by American Physiological Society

ARTICLES

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

X. Xu and K. S. Lee
Upjohn Laboratories, Kalamazoo, Michigan 49007, USA.

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.

This article has been cited by other articles:

				S. J. Liu Inhibition of L-type Ca2+ channel current and negative inotropy induced by arachidonic acid in adult rat ventricular myocytes Am J Physiol Cell Physiol, November 1, 2007; 293(5): C1594 - C1604. [Abstract] [Full Text] [PDF]

				H. Miura, Y. Liu, and D. D. Gutterman Human Coronary Arteriolar Dilation to Bradykinin Depends on Membrane Hyperpolarization : Contribution of Nitric Oxide and Ca2+-Activated K+ Channels Circulation, June 22, 1999; 99(24): 3132 - 3138. [Abstract] [Full Text] [PDF]

				W. B. Campbell and D. R. Harder Endothelium-Derived Hyperpolarizing Factors and Vascular Cytochrome P450 Metabolites of Arachidonic Acid in the Regulation of Tone Circ. Res., March 5, 1999; 84(4): 484 - 488. [Full Text] [PDF]

				H. Miura and D. D. Gutterman Human Coronary Arteriolar Dilation to Arachidonic Acid Depends on Cytochrome P-450 Monooxygenase and Ca2+-Activated K+ Channels Circ. Res., September 7, 1998; 83(5): 501 - 507. [Abstract] [Full Text] [PDF]

				A. Cane, M. Breton, K. Koumanov, G. Bereziat, and O. Colard Oxidant-induced arachidonic acid release and impairment of fatty acid acylation in vascular smooth muscle cells Am J Physiol Cell Physiol, April 1, 1998; 274(4): C1040 - C1046. [Abstract] [Full Text] [PDF]

				S. M. Krischer, M. Eisenmann, A. Bock, and M. J. Mueller Protein-facilitated Export of Arachidonic Acid from Pig Neutrophils J. Biol. Chem., April 18, 1997; 272(16): 10601 - 10607. [Abstract] [Full Text] [PDF]