Propagation of cytosolic calcium waves into the nuclei of hepatocytes

Abstract

The temporal and spatial organization of [Ca 2+] changes within the nucleus of Fura-2 loaded hepatocytes maintained in primary culture has been investigated. Vasopressin stimulation induced oscillatory waves of cytosolic free [Ca 2+] 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 Ca 2+ responses reflect changes occurring within the nucleoplasm. Intranuclear Ca 2+ increases occurred as waves that appear to be directed by the Ca 2+ waves passing through the surrounding cytoplasm. The apparent velocity of Ca 2+ 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 Ca 2+ stores that might be released by Ins(1,4,5)P 3. However, the nuclear envelope functions as a Ca 2+ store that is sensitive to mobilization by Ins(1,4,5)P 3. We conclude that the [Ca 2+] in the nucleoplasm of the hepatocyte is close to equilibrium with the cytosolic [Ca 2+] and that oscillatory waves of cytosolic [Ca 2+] are closely paralleled by similar [Ca 2+] changes in the nucleoplasm. The nuclear envelope is a component of the intracellular Ins(1,4,5)P 3-sensitive Ca 2+ storage pool and may serve as a reservoir for [Ca 2+] elevations within the nucleus.