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

TY - JOUR

T1 - Extracellular Calcium-Dependent Modulation of Endothelium Relaxation in Rat Mesenteric Small Artery

T2 - The Role of Potassium Signaling

AU - Hangaard, Lise

AU - Jessen, Peter B

AU - Kamaev, Dmitrii

AU - Aalkjaer, Christian

AU - Matchkov, Vladimir V

PY - 2015

Y1 - 2015

N2 - 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 (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 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.

AB - 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 (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 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.

U2 - 10.1155/2015/758346

DO - 10.1155/2015/758346

M3 - Journal article

C2 - 26504829

SN - 2314-6133

VL - 2015

SP - 1

EP - 11

JO - BioMed Research International

JF - BioMed Research International

M1 - 758346

ER -