Extracellular Calcium-Dependent Modulation of Endothelium Relaxation in Rat Mesenteric Small Artery: The Role of Potassium Signaling

Abstract

The nature of NO- and COX-independent endothelial hyperpolarization (EDH) is not fully understood but activation of small- and intermittent-conductance Ca2+-activated K+channels (SKCaandIKCa) is important. Previous studies have suggested that the significance ofIKCadepends onCa2+out. Also it has been suggested that K+is important through localizedK+outsignaling causing activation of the Na+,K+-ATPase and inward-rectifying K+channels (Kir). Here we tested the hypothesis that the modulating effect ofCa2+outon the EDH-like response depends onK+out. We addressed this possibility using isometric myography of rat mesenteric small arteries. WhenK+outwas 4.2 mM, relaxation to acetylcholine (ACh) was stronger at 2.5 mMCa2+outthan at 1 mMCa2+out. Inhibition ofIKCawith TRAM34 suppressed the relaxations but did not change the relation between the relaxations at the low and highCa2+out. ThisCa2+out-dependence disappeared at 5.9 mMK+outand in the presence of ouabain or BaCl2. Our results suggest thatIKCaare involved in the localizedK+outsignaling which acts through the Na+,K+-ATPase andKirchannels and that the significance of this endothelium-dependent pathway is modulated byCa2+out.