title: Transient receptor potential canonical type 3 channels: Interactions, role and relevance - A vascular focus.
abstract: Transient receptor potential canonical type 3 channels (TRPC3) are expressed in neural, cardiac, respiratory and vascular tissues, with both similarities and differences between human and animal models for the same cell types. In common with all members of the six subfamilies of TRP channels, TRPC3 are non-voltage gated, non-selective cation channels that are mainly permeated by Ca2+, and have distinct molecular, biophysical, anatomical and functional properties. TRP channels are present in excitable and non-excitable cells where they sense and respond to a wide variety of physical and chemical stimuli. TRPC3 are expressed in the endothelium and/or smooth muscle of specific intact arteries, such as mesenteric, cerebral and myometrial, where they are critical for the control of vascular tone, and show altered activity in development and disease. In artery endothelium, TRPC3 contributes to endothelium-derived hyperpolarization and nitric oxide-mediated vasodilation. In artery smooth muscle, TRPC3 contributes to constrictor mechanisms. In both endothelium and smooth muscle, TRPC3 contributes to function via caveolae-caveolin dependent and independent mechanisms. In different cell types and states, like other TRP channels, TRPC3 can form complexes with other TRP proteins and associated channels and accessory proteins, including those associated with endo(sarco)plasmic reticulum (ER/SR), thereby facilitating Ca2+channel activation and/or refilling ER/SR Ca2+stores. The diversity of TRPC3 interactions with other vascular signaling components is a potential target for artery specific control mechanisms. This brief perspective highlights recent advances in understanding the functional diversity of TRPC3, with an emphasis on vascular health and disease.
authors.affiliation: Inflammation and Healing Cluster, Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Maroochydore, Qld 4558, Australia; Department of Physiology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: t.grayson@unsw.edu.au.
authors.forename: T Hilton
authors.initials: TH
authors.lastname: Grayson
authors.affiliation: Department of Physiology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Timothy V
authors.initials: TV
authors.lastname: Murphy
authors.affiliation: Inflammation and Healing Cluster, Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Maroochydore, Qld 4558, Australia; Department of Physiology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: shaun.sandow@unsw.edu.au.
authors.forename: Shaun L
authors.initials: SL
authors.lastname: Sandow
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013045:Species Specificity; D050052:TRPC Cation Channels / Q000378:metabolism*; D014652:Vascular Diseases / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology
chemical_list: D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D009569:Nitric Oxide; D002118:Calcium
keywords: Artery; Calcium; Endothelium; Ion channel; Smooth muscle