INTRANUCLEAR CA2+ TRANSIENTS DURING NEURITE REGENERATION OF AN ADULT MAMMALIAN NEURON

Depolarization-induced increases in cytoplasmic and intranuclear Ca2+ were visualized in adult mammalian dorsal root ganglion (DRG) neurons during different stages of neurite extension by using confocal laser scanning microscopy and the long-wavelength Ca2+ indicator dye fluo 3-AM (acetoxymethyl ester of fluo 3). In neurons beginning to extend neurites, depolarization led to pronounced increases in nuclear and nucleolar Ca2+ levels severalfold greater than corresponding increases in the cytoplasm. The nucleolar Ca2+ signal often exceeded that of the nucleus, indicating regional heterogeneity of the nucleus. The subcellular calcium transients were dependent on extracellular Ca2+ and the level of depolarization, indicating the importance of transmembrane Ca2+ fluxes in triggering the nuclear events. After neurite extension, the nuclear Ca2+ signals were attenuated and never exceeded cytoplasmic levels. These results indicate that activity-dependent modulation of intranuclear Ca2+ levels is greater in DRG neurons during early neurite extension. Given the importance of Ca2+ in gene expression, the results may be relevant to Ca2+-dependent nuclear events responsible for axonal regeneration.