SOURCE OF NUCLEAR CALCIUM SIGNALS

Transient increases of Ca2+ concentration in the nucleus regulate gene expression and other nuclear processes. We investigated whether nucle ar Ca2+ signals could be regulated independently of the cytoplasm or w ere controlled by cytoplasmic Ca2+ signals. A fluorescent Ca2+ indicat or that is targeted to the nucleus was synthesized by coupling a nucle ar localization peptide to Calcium Green dextran, a 70-kDa Ca2+ indica tor. Stimulation of rat basophilic leukemia cells by antigen or by pho tolytic uncaging of inositol 1,4,5-trisphosphate induced transient inc reases in nuclear and cytosolic Ca2+ concentrations. Elevations in the nuclear Ca2+ concentration followed those in the nearby perinuclear c ytosol within 200 ms. Heparin-dextran, an inhibitor of the inositol 1, 4,5-trisphosphate receptor that is excluded from the nucleus, was synt hesized to specifically block the release of Ca2+ from cytosolic store s. Addition of this inhibitor suppressed Ca2+ transients in the nucleu s and the cytosol. We conclude that the Ca2+ level in the nucleus is n ot independently controlled. Rather, nuclear Ca2+ increases follow cyt osolic Ca2+ increases with a short delay most likely due to Ca2+ diffu sion from the cytosol through the nuclear pores.