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 (SKCa and IKCa) is important. Previous studies have suggested that the significance of IKCa 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 (Kir). 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 IKCa 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 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 [Ca(2+)]out.
MEMBRANES, Department of Biomedicine, Health, Aarhus University, 8000 Aarhus, Denmark.
Lise
L
Hangaard
MEMBRANES, Department of Biomedicine, Health, Aarhus University, 8000 Aarhus, Denmark.
Peter B
PB
Jessen
MEMBRANES, Department of Biomedicine, Health, Aarhus University, 8000 Aarhus, Denmark.
Dmitrii
D
Kamaev
MEMBRANES, Department of Biomedicine, Health, Aarhus University, 8000 Aarhus, Denmark ; Department of Biomedicine, University of Copenhagen, Copenhagen, Denmark.
Christian
C
Aalkjaer
MEMBRANES, Department of Biomedicine, Health, Aarhus University, 8000 Aarhus, Denmark.
Vladimir V
VV
Matchkov
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D017609:Barium Compounds; D002118:Calcium / Q000494:pharmacology*; D002712:Chlorides; D004791:Enzyme Inhibitors; D008638:Mesenteric Arteries / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D017609:Barium Compounds; D002712:Chlorides; D004791:Enzyme Inhibitors; C024986:barium chloride; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine