Stimulation of arterial 42K efflux by ATP depletion and cromakalim is antagonized by glyburide.
It has been suggested that cromakalim (BRL 34915)-induced vasorelaxation was associated with stimulation of ATP-sensitive K channels. The hyperpolarization resulting from activation of this mechanism might then inhibit voltage-dependent Ca2+ entry and subsequent contraction. The present study evaluated the similarities of 42K efflux stimulated by ATP depletion (verified by high-performance liquid chromatography) and by exposure to cromakalim (10 microM) in rabbit superior mesenteric arteries. Both depletion of intracellular ATP and exposure to cromakalim significantly stimulated 42K efflux (P less than 0.05). Glyburide (a selective inhibitor of ATP-sensitive K channels in pancreatic beta-cells) inhibited 42K efflux stimulated by ATP depletion and by cromakalim exposure. Glyburide (10 microM) had no significant effect on either basal 42K or the 42K efflux stimulated by norepinephrine and by K depolarization, which cause voltage and Ca2(+)-dependent activation of K channels. Glyburide therefore had a relatively selective effect on vascular smooth muscle. The glyburide-sensitive 42K efflux during ATP depletion and exposure to cromakalim was greatest in Ca2(+)-free solution (Mg raised to 10 mM). We conclude that in vascular smooth muscle both depletion of ATP and exposure to cromakalim stimulate 42K efflux via a glyburide-sensitive mechanism with properties similar to those of ATP-sensitive K channels observed in cardiac and pancreatic beta-cells.
Post
J M
JM
Department of Physiology, University of Missouri School of Medicine, Columbia 65212.
Jones
A W
AW
D000255:Adenosine Triphosphate / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D001158:Arteries / Q000378:metabolism*; D001578:Benzopyrans / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019806:Cromakalim; D005905:Glyburide / Q000494:pharmacology*; D008297:Male; D011188:Potassium / Q000378:metabolism*; D011197:Potassium Radioisotopes; D011758:Pyrroles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D011197:Potassium Radioisotopes; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D000255:Adenosine Triphosphate; D011188:Potassium; D005905:Glyburide