title: ATP promotes NCX-reversal in aortic smooth muscle cells by DAG-activated Na+ entry.
abstract: Reversal of the plasma membrane Na(+)/Ca(2+) exchanger (NCX) has been shown to mediate Ca(2+) influx in response to activation of G-protein linked receptors. Functional coupling of reverse-mode NCX with canonical transient receptor potential channels (TRPC), specifically TRPC6, has recently been demonstrated by our laboratory to mediate Ca(2+) influx in rat aortic smooth muscle cells (RASMCs) following ATP stimulation. In this communication, we provide further detail of this functional coupling by indirectly measuring NCX reversal. We found that NCX reversal, induced by the removal of extracellular Na(+), was increased following stimulation with ATP and the diacylglycerol analog 1-Oleoyl-2-acetyl-sn-glycerol. This increased NCX reversal was attenuated by SKF-96365, an inhibitor of non-selective cation channels, and by activation of protein kinase C with phorbol ester 12-tetradecanoylphorbol-13 acetate. These data are consistent with the known properties of TRPC6 and further support that functional coupling of TRPC6 and NCX occurs via a receptor-operated, rather than store-operated, cascade in RASMCs.
authors.affiliation: Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, BC, Canada V6T 1Z1.
authors.forename: Harley T
authors.initials: HT
authors.lastname: Syyong
authors.forename: Damon
authors.initials: D
authors.lastname: Poburko
authors.forename: Nicola
authors.initials: N
authors.lastname: Fameli
authors.forename: Cornelis
authors.initials: C
authors.lastname: van Breemen
mesh_terms: D000255:Adenosine Triphosphate / Q000008:administration & dosage*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
chemical_list: D019831:Sodium-Calcium Exchanger; D000255:Adenosine Triphosphate; D012964:Sodium; D002118:Calcium