ATP-dependent accumulation and inositol trisphosphate- or cyclic ADP-ribose-mediated release of Ca 2+ from the nuclear envelope

Abstract

Uptake and release of Ca 2+ from isolated liver nuclei were studied with fluorescent probes. We show with the help of digital imaging and confocal microscopy that the Ca 2+-sensitive fluorescent probe Fura 2 is concentrated in or around the nuclear envelope and that the distribution of Fura 2 fluorescence is similar to that of an endoplasmic reticulum marker. The previously demonstrated ATP-dependent uptake of Ca 2+ into isolated nuclei and release of the accumulated Ca 2+ by inositol 1,4,5-trisphosphate (IP 3) are therefore due to transport of Ca 2+ into and out of the nuclear envelope and not the nucleoplasm. Dextrans labeled with fluorescent Ca 2+ indicators (calcium-Green 1 and Fura 2) are distributed uniformly in the nucleoplasm and can be used to show that changes in the external Ca 2+ concentration produce rapid changes in the nucleoplasmic Ca 2+ concentration. Nevertheless, IP 3 and cyclic ADP-ribose evoke transient intranuclear Ca 2+ elevations. The release from the Ca 2+ stores in or around the nuclear envelope appears to be directed into the nucleoplasm from where it can diffuse out through the permeable nuclear pore complexes.