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 μm/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.