Changes in either cytosolic or nucleoplasmic inositol 1,4,5-trisphosphate levels can control nuclear Ca2+...

The free nucleoplasmic Ca2+ concentration ([Ca2+]n) may regulate many nuclear events, such as gene transcription. Since the nucleus may possess the enzymes necessary to generate the second messenger inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), and because the nuclear envelope may enclose an Ins(1,4,5)P3-releasable Ca2+ store, we tested the hypothesis that nuclear and/or cytosolic levels of Ins(1,4,5)P3 can control [Ca2+]n. To assay [Ca2+]n, we measured the fluorescence of the Ca2+ indicator fluo 3 in the nucleus of Xenopus oocytes by confocal microscopy. When we injected Ins(1,4,5)P3 into the cytosol, [Ca2+]n increased. This increase in [Ca2]n still occurred when heparin was present in the nucleus, but was abolished when heparin was present in the cytosol, indicating that cytosolic Ins(1,4,5)P3 levels could control [Ca2+]n. When we injected Ins(1,4,5)P3 directly into the nucleus, [Ca2+]n increased, even when heparin was present in the cytosol, indicating that Ins(1,4,5)P3 could control [Ca2+]n from within the nucleus. These results provide functional evidence for Ins(1,4,5)P3 receptors facing the nucleoplasm and raise the possibility that a phosphoinositide cycle situated at the nuclear membranes can control Ca(2+)-dependent nuclear functions.