title: Na,K-ATPase generates calcium oscillations in hippocampal astrocytes.
abstract: Na,K-ATPase maintains not only ionic homeostasis, but also participates in a multiprotein complex mediating intracellular signalling. We show that ouabain, a specific ligand for Na,K-ATPase, evokes calcium oscillations in hippocampal astrocytes in primary cultures. Coimmunoprecipitation studies suggest that the mechanism underlying these calcium oscillations involves a multiprotein complex consisting of ankyrin-B, the inositol 1,4,5-trisphosphate receptor and Na,K-ATPase. The ouabain/Na,K-ATPase multi-protein complex induced calcium-dependent downstream activation of the transcription factor nuclear factor-kappaB. Calcium oscillations and nuclear factor-kappaB activation were blocked following intracellular calcium store depletion. Thus, the specific Na,K-ATPase ligand ouabain induced inositol 1,4,5-trisphosphate receptor-dependent calcium oscillations in hippocampal astrocytes, which mediates nuclear factor-kappaB activation.
authors.affiliation: Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Xiao Li
authors.initials: XL
authors.lastname: Liu
authors.forename: Ayako
authors.initials: A
authors.lastname: Miyakawa
authors.forename: Anita
authors.initials: A
authors.lastname: Aperia
authors.forename: Patrik
authors.initials: P
authors.lastname: Krieger
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000201:enzymology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009284:Naphthols; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014227:Triazines
chemical_list: C409762:2-(3-aminophenol)-6-(4-amino-1-naphthol)-4-chloro-triazine; C490614:Ank3 protein, rat; D017487:Ankyrins; D004791:Enzyme Inhibitors; D053496:Inositol 1,4,5-Trisphosphate Receptors; D046912:Multiprotein Complexes; D016328:NF-kappa B; D009284:Naphthols; D014227:Triazines; D018698:Glutamic Acid; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium