Ontogeny of ATP hydrolysis and isoform expression of the Plasma Membrane Ca(2+)-ATPase in mouse brain

BACKGROUND: Plasma membrane Ca(2+)-ATPases (PMCAs) are high affinity Ca(2+ )transporters actively involved in intracellular Ca(2+ )homeostasis. Considering the critical role of Ca(2+ )signalling in neuronal development and plasticity, we have analyzed PMCA-mediated Ca(2+)-ATPase activity and PMCA-isoform content in membranes from mouse cortex, hippocampus and cerebellum during postnatal development. RESULTS: PMCA activity was detected from birth, with a faster evolution in cortex than in hippocampus and cerebellum. Western blots revealed the presence of the four isoforms in all regions, with similar increase in their expression patterns as those seen for the activity profile. Immunohistochemistry assays in cortex and hippocampus showed co-expression of all isoforms in the neuropil associated with synapses and in the plasma membrane of pyramidal cells soma, while cerebellum showed a more isoform-specific distribution pattern in Purkinje cells. CONCLUSION: These results show an upregulation of PMCA activity and PMCA isoforms expression during brain development in mouse, with specific localizations mainly in cerebellum. Overall, our findings support a close relationship between the ontogeny of PMCA isoforms and specific requirements of Ca(2+ )during development of different brain areas.