Vasopressin-induced cytoplasmic and nuclear calcium signaling in embryonic cortical astrocytes: Dynamics of calcium and calcium-dependent kinase translocation

The present study sought to determine the downstream consequences of V_1a vasopressin receptor (V_1aR) activation of Ca²⁺ signaling in cortical astrocytes. Results of these analyses demonstrated that V_1aR activation led to a marked increase in both cytoplasmic and nuclear Ca²⁺. We also investigated V_1aR activation of Ca²⁺-activated signaling kinases, protein kinase C (PKC), Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), and the mitogen-activated protein (MAP) kinases [MAPK and extracellular signal-regulated kinases 1 and 2 (ERK1/2)], their localization within cytoplasmic and nuclear compartments, and activation of their downstream nuclear target, the transcription factor cAMP response element-binding protein (CREB). Results of these analyses demonstrated that V_1aR activation led to a significant rise in PKC, CaMKII, and ERK1/2 activation, with CaMKII and ERK1/2 demonstrating dynamic transport between cytoplasmic and nuclear compartments. Although no evidence of PKC translocation was apparent, PKC and CaMKs were required for activation and nuclear translocation of ERK1/2. Subsequent to CaMKII and ERK1/2 translocation to the nucleus, CREB activation occurred and was found to be dependent on upstream activation of ERK1/2 and CaMKs. These data provide the first systematic analysis of the V_1aR-induced Ca²⁺ signaling cascade in cortical astrocytes. In addition, results of this study introduce a heretofore unknown effect of vasopressin, dynamic Ca²⁺ signaling between the cytoplasm and nucleus that leads to comparable dynamics of kinase activation and shuttling between cytoplasmic and nuclear compartments. Implications for development and regeneration induced by V_1aR activation of CREB-regulated gene expression in cortical astrocytes are discussed.