title: Ca2+ signaling in smooth muscle: TRPC6, NCX and LNats in nanodomains.
abstract: Following the recent observation of localized cytosolic subplasmalemmal [Na+] elevations (LNats) in rat aortic smooth muscle cells, we discuss here the current evidence for the structural and molecular roles of cytosolic nanodomains at close junctions of the plasma membrane (PM) and sarcoplasmic reticulum (SR) in the generation of LNats. These junctions, the loss of which might contribute to vascular aging and disease, provide a platform for ion metabolism signalplexes and the interaction of localized Na+ and Ca2+ gradients. We moreover suggest the existence in the junctions of a Na+ diffusional barrier as a necessary condition for the generation of LNats. LNats are likely a fundamental feature of near membrane ion signaling in many cell types, and their discovery offers new possibilities for elucidating the mechanism, function and pathogenesis of Na+ and Ca2+ signaling nanodomains.
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Damon
authors.initials: D
authors.lastname: Poburko
authors.forename: Nicola
authors.initials: N
authors.lastname: Fameli
authors.forename: Kuo-Hsing
authors.initials: KH
authors.lastname: Kuo
authors.forename: Cornelis
authors.initials: C
authors.lastname: van Breemen
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004058:Diffusion; D007477:Ions; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D017434:Protein Structure, Tertiary; D011817:Rabbits; D051381:Rats; D015398:Signal Transduction; D012964:Sodium / Q000737:chemistry; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000378:metabolism / Q000502:physiology*
chemical_list: D007477:Ions; D019831:Sodium-Calcium Exchanger; D050052:TRPC Cation Channels; C492145:Trpc6 protein, rat; D012964:Sodium; D002118:Calcium