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.
Lin
C
C
Department of Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Hajnóczky
G
G
Thomas
A P
AP
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism*; D016257:Fura-2; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008856:Microscopy, Fluorescence; D051381:Rats; D017207:Rats, Sprague-Dawley
D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium; D016257:Fura-2