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 ( SKCa and IKCa ) is important. Previous studies have suggested that the significance of IKCa depends on Ca2+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 ( Kir ). Here we tested the hypothesis that the modulating effect of Ca2+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 Ca2+out than at 1 mM Ca2+out . Inhibition of IKCa with TRAM34 suppressed the relaxations but did not change the relation between the relaxations at the low and high Ca2+out . This Ca2+out -dependence disappeared at 5.9 mM K+out and in the presence of ouabain or BaCl 2 . Our results suggest that IKCa are involved in the localized K+out signaling which acts through the Na + ,K + -ATPase and Kir channels and that the significance of this endothelium-dependent pathway is modulated by Ca2+out .
Hangaard, L., Jessen, P. B., Kamaev, D., Aalkjaer, C., & Matchkov, V. V. (2015). Extracellular Calcium-Dependent Modulation of Endothelium Relaxation in Rat Mesenteric Small Artery: The Role of Potassium Signaling. BioMed Research International, 2015. https://doi.org/10.1155/2015/758346