Effect of Kil769, a Novel K+-channel Opener, on Sensitivity to Ca2+ of Contractile Elements and Inositol Phosphate Formation in Porcine Coronary Artery

Abstract

Abstract To determine whether Kil769, a novel K+-channel opener, acts intracellularly in vasorelaxation, we compared the effects of Kil 769 on force of contraction, intracellular Ca2+ concentration ([Ca2+]i) and inositol phosphate (IP1) formation with those of Ca2+-channel blockers in isolated porcine coronary artery. Kil 769 (10 μm) and verapamil (1 μm), which produced submaximal relaxation, reduced the increase in [Ca2+]i and force of contraction induced by 25 mM KC1. Verapamil reduced [Ca2+]i and the force of contraction to a similar extent but Kil 769 reduced force of contraction more strongly than it did [Ca2+]i. Kil 769 also inhibited U46619 (9,11-dideoxy-9α, 11α-methano-epoxy-PGF2a)-induced IP1 formation and glibenclamide blocked its inhibitory effect. These results suggest that the opening of K+ channels induced by Kil 769 reduces the Ca2+ sensitivity of contractile elements and inositol phospholipid hydrolysis which is related to the Ca2+ release from intracellular storage.