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

Abstract EN

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 ( 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 BaCl2.

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 .