APStracts 2:0509H, 1995.

Dual effects of arachidonic acid on atp-sensitive k+ current of coronary smooth muscle cells. Xu, Xiaoping, and Kai S. Lee. Cardiovascular Pharmacology, Upjohn Laboratories, Kalamazoo, MI 49007

APStracts 2:0509H, 1995.

ATP-sensitive K-channels (KATP) 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 KATP channel of dog coronary artery smooth muscle cells using the whole -cell voltage-clamp technique. AA was found to have dual effects on the KATP current. In cells dialyzed with 1 mM ATP pipette solution, external application of AA activated the KATP current with a bell -shaped concentration-response curve. The KATP current measured at -50 mV was 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. In contrast, if the KATP current was activated by dialyzing the cell with ATP-free pipette solution to begin with, external application of AA at concentrations from 2 to 16 [mu]M concentration-dependently inhibited the KATP current (IC50 = 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 non-metabolizable analogue of AA, also produced dual effects on the KATP current. 4 [mu]M ETYA increased the KATP current measured at -50 mV from 2.9 +/- 1.2 to 37 +/- 7 pA in 1 mM intracellular ATP (ATPi), whereas 8 [mu]M ETYA inhibited the KATP current in 0 mM ATPi by 71 +/- 3%. These results suggest that the dual effects of AA on the KATP current of dog coronary smooth muscle cells do not require AA metabolism. The activation of KATP channels in smooth muscle cells may contribute to the AA induced coronary vasodilation.

Received 23 January 1995; accepted in final form 26 October 1995.
APS Manuscript Number H60-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95