Activation of phospholipase C by the agonist U46619 is inhibited by cromakalim-induced hyperpolarization in porcine coronary artery.

We measured inositol 1,4,5-trisphosphate (IP3) production, intracellular calcium concentration ([Ca2+]i) and force of contraction induced by a thromboxane A2 analogue U46619 in porcine coronary artery to elucidate the relaxant effect of a K+ channel opener cromakalim. Cromakalim (10 microM) significantly inhibited the production of IP3, Ca2+ release from intracellular stores and contraction induced by 300 nM U46619. The inhibitory effect of cromakalim on IP3 was blocked by a K+ channel blocker tetrabutylammonium (TBA, 3 mM) and counteracted by 20 mM KCl-induced depolarization. These results suggest that the hyperpolarization of the plasma membrane by cromakalim inhibits the activation of phospholipase via the stimulation of the thromboxane A2 receptor to result in vasodilation.