Electron microscopy localization of NCX1, 2, 3 isoform protein exchangers in neuronal astrocytes.

Na + /Ca 2+ exchangers (NCX1, 2 and 3) play relevant role in neural cells, where variations of cytosolic Ca 2+ concentration represent a pivotal event in many physiological and pathological processes. Astrocytes display a type of excitability based on changes in intracellular Ca 2+ concentration. In the present study, electron microscopic immunohistochemistry was applied to investigate the expression of the three NCX1-3 protein isoforms, in astrocytes of cerebral cortex and hippocampus. Results showed that a conspicuous population of astrocytic cells expressed NCX1–3 in both brain areas. Immunolabeling for NCX1-3 was observed in many glial profiles of various size, notably in distal astrocytic processes in contiguity of synaptic structures, suggesting the involvement of NCX in shaping astrocytic [Ca]i transients evoked by adjacent synaptic activity. NCX1-3 immunoreactivities (irs) were expressed in astrocytic mitochondria, indicating an important contribution to mitochondrial Ca 2+ regulation in this cell type in situ. In addition, all NCX isoforms were consistently expressed in perivascular astrocytic endfeet, suggesting an important role in regulating the barrier function of blood-brain barrier (BBB). Present immunomorphological work showed that in both brain regions all NCX isoforms were expressed in astrocytes, thus pointing to a widespread role of the three exchangers in maintaining Ca 2+ homeostasis in glial cells and suggesting that distinct NCX isoforms may share analogous physiological roles in the brain in vivo.