CHANGES IN EITHER CYTOSOLIC OR NUCLEOPLASMIC INOSITOL 1,4,5-TRISPHOSPHATE LEVELS CAN CONTROL NUCLEAR CA2+ CONCENTRATION

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)P-3), and because the nuclear envelope may enclose an Ins(1,4,5)P-3-releasable Ca2+ store, we tested the hypothesis that nuclear and/or cytosolic levels of Ins(1,4,5)P-3 can control [Ca2+](n). To assay [Ca2+](n), we measured the fluorescence of the Ca2+ indicator flue 3 in the nucleus of Xenopus oocytes by confocal microscopy. When we injected Ins(1,4,5)P-3 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)P-3 levels could control [Ca2+](n). When we injected Ins(1,4,5)P-3 directly into the nucleus, [Ca2+](n) increased, even when heparin was present in the cytosol, indicating that Ins(1,4,5)P-3 could control [Ca2+](n)fa from within the nucleus. These results provide functional evidence for Ins(1,4,5)P-3 receptors facing the nucleoplasm and raise the possibility that a phosphoinositide cycle situated at the nuclear membranes can control Ca2+-dependent nuclear functions.