ATP stimulates Ca2+ uptake and increases the free Ca2+ concentration in isolated rat liver nuclei

P. Nicotera, D. J. McConkey, D. P. Jones, S. Orrenius

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Addition of ATP to a highly purified fraction of rat liver nuclei incubated with submicromolar concentrations of Ca2+ and trace amounts of 45Ca2+ resulted in the rapid accumulation of 45Ca2+ in the nuclei. This was associated with an increase in intranuclear free Ca2+ concentration as measured with the fluorescent dye 1-[2-(5-carboxyoxazol-2-yl)-6-aminobenzofuran-5-oxy]-2-(2'-amino-5'-me0 thylphenoxy)ethane-N,N,N',N'-tetraacetic acid (fura-2). Inhibitors of microsomal and mitochondrial Ca2+ translocases had no effect on nuclear Ca2+ sequestration, indicating that it was distinct from previously known intracellular Ca2+-transporting systems. Ca2+ uptake and the associated increase in intranuclear free Ca2+ concentration were prevented by calmidazolium, a potent calmodulin antagonist. Partial characterization of the ATP-stimulated nuclear Ca2+ uptake showed that maximal rates of Ca2+ uptake and increase in intranuclear free Ca2+ level occurred at concentrations of Ca2+ normally present in the cytosol of mammalian cells. Together, these results show that a distinct, ATP- and calmodulin-dependent Ca2+ uptake system exists in liver nuclei. This system may play an important role in the regulation of intranuclear Ca2+-dependent processes.

Original languageEnglish (US)
Pages (from-to)453-457
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number2
StatePublished - 1989
Externally publishedYes

ASJC Scopus subject areas

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