Invited Symposium: Molecular Physiology of Sodium-Calcium Exchange
The Na+/Ca2+ exchanger is expressed exclusively in the distal nephron in kidney, and plays a major role in the basolateral exit of calcium in this segment. Studies in isolated membrane vesicles have shown that the exchanger is regulated by PTH. NCX-1, the first member of the Na+/Ca2+ exchanger gene family cloned, is widely expressed in many tissues including kidney, and a variety of tissue-specific alternatively spliced isoforms have been described. In order to evaluate the molecular mechanisms responsible for the regulation of the renal Na+/Ca2+ exchanger we stably transfected OK-P cells with two kidney-specific isoforms (NACA2 and -3). Subclones of the parent cell line were isolated based on transport activity, and immunofluorescence with an exchanger specific monoclonal antibody. PTH acutely stimulated Na+-dependent calcium uptake in a dose-dependent fashion, with a 1/2 maximal concentration of 0.7 nM. The PTH-induced increase in Na+/Ca2+ exchange activity was completely blocked by the protein kinase C inhibitor chelerythrine. The protein kinase A inhibitor H-89 had no effect. In addition, the PTH stimulation of cAMP could be dissociated from that of the Na+/Ca2+ exchanger. PTH stimulated cAMP at a 1/2 maximal concentration that is approximately 40 times higher (30 nM) than that required for 1/2 maximal stimulation of the exchanger. These data suggest that protein kinase C and not protein kinase A participates in the signaling pathways that regulate the renal Na+/Ca2+ exchanger.
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|Reilly, RF; (1998). Parathyroid Hormone (PTH)-Stimulated Na/Ca Exchange is Blocked by Inhibitors of Protein Kinase C but not by Inhibitors of Protein Kinase A in a Novel Transfected Cell Line. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/lytton/reilly0733/index.html|
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