Propagation of cytosolic calcium waves into the nuclei of hepatocytes.

The temporal and spatial organization of [Ca2+] changes within the nucleus of Fura-2 loaded hepatocytes maintained in primary culture has been investigated. Vasopressin stimulation induced oscillatory waves of cytosolic free [Ca2+] increase, which propagated freely through the nuclear region. Based on the amplitude of the Fura-2 signals from this region, the morphology of the hepatocyte nucleus and the rapid penetration of the nucleus by injected Fura-2, it can be concluded that the nuclear Ca2+ responses reflect changes occurring within the nucleoplasm. Intranuclear Ca2+ increases occurred as waves that appear to be directed by the Ca2+ waves passing through the surrounding cytoplasm. The apparent velocity of Ca2+ waves was higher in the nucleoplasm than in the cytoplasm (19.5 +/- 2.9 versus 11.0 +/- 1.1 microns/s). The nucleoplasm does not contain vesicular Ca2+ stores that might be released by Ins(1,4,5)P3. However, the nuclear envelope functions as a Ca2+ store that is sensitive to mobilization by Ins(1,4,5)P3. We conclude that the [Ca2+] in the nucleoplasm of the hepatocyte is close to equilibrium with the cytosolic [Ca2+] and that oscillatory waves of cytosolic [Ca2+] are closely paralleled by similar [Ca2+] changes in the nucleoplasm. The nuclear envelope is a component of the intracellular Ins(1,4,5)P3-sensitive Ca2+ storage pool and may serve as a reservoir for [Ca2+] elevations within the nucleus.