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

The nature of NO- and COX-independent endothelial hyperpolarization (EDH) is not fully understood but activation of small- and intermittent-conductance Ca(2+)-activated K(+) channels (SK(Ca) and IK(Ca)) is important. Previous studies have suggested that the significance of IK(Ca) depends on [Ca(2+)](out). Also it has been suggested that K(+) is important through localized [K(+)](out) signaling causing activation of the Na(+),K(+)-ATPase and inward-rectifying K(+) channels (K(ir)). Here we tested the hypothesis that the modulating effect of [Ca(2+)](out) on the EDH-like response depends on [K(+)](out). We addressed this possibility using isometric myography of rat mesenteric small arteries. When [K(+)](out) was 4.2 mM, relaxation to acetylcholine (ACh) was stronger at 2.5 mM [Ca(2+)](out) than at 1 mM [Ca(2+)](out). Inhibition of IK(Ca) with TRAM34 suppressed the relaxations but did not change the relation between the relaxations at the low and high [Ca(2+)](out). This [Ca(2+)](out)-dependence disappeared at 5.9 mM [K(+)](out) and in the presence of ouabain or BaCl(2). Our results suggest that IK(Ca) are involved in the localized [K(+)](out) signaling which acts through the Na(+),K(+)-ATPase and K(ir) channels and that the significance of this endothelium-dependent pathway is modulated by [Ca(2+)](out).