Premium
Changes in the expression of plasma membrane calcium extrusion systems during the maturation of hippocampal neurons
Author(s) -
Kip Sertac N.,
Gray Noah W.,
Burette Alain,
Canbay Ali,
Weinberg Richard J.,
Strehler Emanuel E.
Publication year - 2006
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.20129
Subject(s) - plasma membrane ca2+ atpase , microbiology and biotechnology , hippocampal formation , downregulation and upregulation , calcium pump , neuropil , calcium in biology , calcium signaling , neurite , growth cone , biology , chemistry , intracellular , neuroscience , atpase , biochemistry , in vitro , central nervous system , axon , gene , enzyme
Spatial and temporal control of intracellular calcium signaling is essential for neuronal development and function. The termination of local Ca 2+ signaling and the maintenance of basal Ca 2+ levels require specific extrusion systems in the plasma membrane. In rat hippocampal neurons (HNs) developing in vitro, transcripts for all isoforms of the plasma membrane Ca 2+ pump and the Na/Ca 2+ exchanger, and the major nonphotoreceptor Na + /Ca 2+ ,K + exchangers (NCKX) were strongly upregulated during the second week in culture. Upregulation of plasma membrane calcium ATPases (PMCAs)1, 3, and 4 mRNA coincided with a splice shift from the ubiquitous b‐type to the neuron‐specific a‐type with altered calmodulin regulation. Expression of all PMCA isoforms increased over 5‐fold during the first 2 weeks. PMCA immunoreactivity was initially concentrated in the soma and growth cones of developing HNs. As the cells matured, PMCAs concentrated in the dendritic membrane and often colocalized with actin‐rich dendritic spines in mature neurons. In the developing rat hippocampal CA1 region, immunohistochemistry confirmed the upregulation of all PMCAs and showed that by the end of the second postnatal week, PMCAs1, 2, and 3 were concentrated in the neuropil, with less intense staining of cell bodies in the pyramidal layer. PMCA4 staining was restricted to a few cells showing intense labeling of the cell periphery and neurites. These results establish that all major Ca 2+ extrusion systems are strongly upregulated in HNs during the first 2 weeks of postnatal development. The overall increase in Ca 2+ extrusion systems is accompanied by changes in the expression and cellular localization of different isoforms of the Ca 2+ pumps and exchangers. The accumulation of PMCAs in dendrites and dendritic spines coincides with the functional maturation in these neurons, suggesting the importance of the proper spatial organization of Ca 2+ extrusion systems for synaptic function and development. © 2005 Wiley‐Liss, Inc.