title: Transient receptor potential canonical type 3 channels control the vascular contractility of mouse mesenteric arteries.
abstract: Transient receptor potential canonical type 3 (TRPC3) channels are non-selective cation channels and regulate intracellular Ca2+ concentration. We examined the role of TRPC3 channels in agonist-, membrane depolarization (high K+)-, and mechanical (pressure)-induced vasoconstriction and vasorelaxation in mouse mesenteric arteries. Vasoconstriction and vasorelaxation of endothelial cells intact mesenteric arteries were measured in TRPC3 wild-type (WT) and knockout (KO) mice. Calcium concentration ([Ca2+]) was measured in isolated arteries from TRPC3 WT and KO mice as well as in the mouse endothelial cell line bEnd.3. Nitric oxide (NO) production and nitrate/nitrite concentrations were also measured in TRPC3 WT and KO mice. Phenylephrine-induced vasoconstriction was reduced in TRPC3 KO mice when compared to that of WT mice, but neither high K+- nor pressure-induced vasoconstriction was altered in TRPC3 KO mice. Acetylcholine-induced vasorelaxation was inhibited in TRPC3 KO mice and by the selective TRPC3 blocker pyrazole-3. Acetylcholine blocked the phenylephrine-induced increase in Ca2+ ratio and then relaxation in TRPC3 WT mice but had little effect on those outcomes in KO mice. Acetylcholine evoked a Ca2+ increase in endothelial cells, which was inhibited by pyrazole-3. Acetylcholine induced increased NO release in TRPC3 WT mice, but not in KO mice. Acetylcholine also increased the nitrate/nitrite concentration in TRPC3 WT mice, but not in KO mice. The present study directly demonstrated that the TRPC3 channel is involved in agonist-induced vasoconstriction and plays important role in NO-mediated vasorelaxation of intact mesenteric arteries.
authors.affiliation: Department of Physiology and BK21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Soo-In
authors.initials: SI
authors.lastname: Yeon
authors.affiliation: Department of Pharmacology and BK21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Physiology, Kwandong University College of Medicine, Gangneung, Korea.
authors.forename: Dong-Soo
authors.initials: DS
authors.lastname: Yeon
authors.affiliation: Laboratory of Neurobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America.
authors.forename: Joel
authors.initials: J
authors.lastname: Abramowitz
authors.affiliation: Laboratory of Neurobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America.
authors.forename: Lutz
authors.initials: L
authors.lastname: Birnbaumer
authors.affiliation: Epithelial Signaling and Transport Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Shmuel
authors.initials: S
authors.lastname: Muallem
authors.affiliation: Department of Physiology and BK21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Lee
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D008638:Mesenteric Arteries / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D050052:TRPC Cation Channels / Q000235:genetics* / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects / Q000235:genetics*; D014664:Vasodilation / Q000187:drug effects / Q000235:genetics
chemical_list: D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D009569:Nitric Oxide; D000109:Acetylcholine; D002118:Calcium