Regulation of nuclear calcium uptake by inositol phosphates and external calcium

Factors affecting Ins(1,3,4,5)P₄-mediated nuclear Ca²⁺ uptake are investigated, which include Ins(1,3,4,5)P₄ receptor ligand specificity and free external Ca²⁺ concentrations. Among various inositol phosphates examined, Ins(1,3,4,6)P₄, Ins(3,4,5,6)P₄, and Ins(1,3,4,5,6)P₅ can also stimulate ⁴⁵Ca²⁺ influx into isolated rat liver nuclei by activating the Ins(1,3,4,5)P₄ receptor-mediated Ca²⁺ uptake into the nucleus. The EC₅₀ values of these polyphosphates range between 200 and 300 nM, which are 3-4 folds higher than that of Ins(1,3,4,5)P₄. It is plausible that these polyphosphates in conjunction with Ins(1,3,4,5)P₄ take part in the regulation of nuclear Ca²⁺ uptake in view of their intracellular levels during cell activation. Moreover, the inositol phosphate-induced Ca²⁺ uptake is facilitated by increasing Ca²⁺ levels in the uptake milieu, suggesting a possible link between cytosolic and nuclear Ca²⁺ signals through the Ins(1,3,4,5)P₄ receptor.