Altered acetylcholine, bradykinin and cutaneous pressure-induced vasodilation in mice lacking the TREK1 potassium channel: the endothelial link.
The TWIK related K+ channel TREK1 is an important member of the class of two-pore-domain K+ channels. It is a background K+ channel and is regulated by hormones, neurotransmitters, intracellular pH and mechanical stretch. This work shows that TREK1 is present both in mesenteric resistance arteries and in skin microvessels. It is particularly well expressed in endothelial cells. Deletion of TREK1 in mice leads to an important alteration in vasodilation of mesenteric arteries induced by acetylcholine and bradykinin. Iontophoretic delivery of acetylcholine and bradykinin in the skin of TREK1+/+ and TREK1-/- mice also shows the important role of TREK1 in cutaneous endothelium-dependent vasodilation. The vasodilator response to local pressure application is also markedly decreased in TREK1-/- mice, mimicking the decreased response to pressure observed in diabetes. Deletion of TREK1 is associated with a marked alteration in the efficacy of the G-protein-coupled receptor-associated cascade producing NO that leads to major endothelial dysfunction.
Garry
Ambroise
A
Biologie Neuro-vasculaire Intégrée, UMR CNRS 6214-INSERM 771, Faculté de Médecine Angers, 49045 Angers, France.
Fromy
Bérengère
B
Blondeau
Nicolas
N
Henrion
Daniel
D
Brau
Frédéric
F
Gounon
Pierre
P
Guy
Nicolas
N
Heurteaux
Catherine
C
Lazdunski
Michel
M
Saumet
Jean Louis
JL
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics*; D001920:Bradykinin / Q000494:pharmacology; D002196:Capillaries / Q000737:chemistry / Q000187:drug effects; D004730:Endothelium, Vascular / Q000737:chemistry / Q000502:physiology*; D017353:Gene Deletion; D008638:Mesenteric Arteries / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009569:Nitric Oxide / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011312:Pressure; D012867:Skin / Q000098:blood supply; D014664:Vasodilation / Q000235:genetics*
D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; D009569:Nitric Oxide; D000109:Acetylcholine; D001920:Bradykinin