Nuclear calcium regulation by inositol phosphates and cyclic ADP-ribose

Nuclear Ca²⁺ is independent of cytosolic Ca²⁺, of which the regulatory mechanism remains unclear. Several lines of evidence indicate that inositol phosphates take part in the regulation of Ca2⁺ transport across nuclear membranes. For instance, Ins(T,3,4,5)P4 and Ins(l,4,5)P3 have been implicated in nuclear Ca2⁺ uptake and release, respectively, through ligand-gated Ca2⁺ channels. Using rat liver nuclei, we assessed the effect of various inositol phosphates and cyclic ADP-ribose (cADPR) on nuclear Ca2⁺ uptake. It was found that most high inositol polyphosphates, such as InsP4s, Ins(l,3,4,5,6)P, and InsP6, as well as cADPR were able to facilitate nuclear "Ca uptake with potencies comparable to or even greater than that of Ins(l,3,4,5)P4. Considering that IP. and IP6 exist in cells in considerably higher concentrations than Ins(l,3,4,5)P4, they may also play an important role in nuclear Ca2⁺ reeulation.