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International Journal of Cell Biology
Volume 2014, Article ID 152645, 12 pages
http://dx.doi.org/10.1155/2014/152645
Research Article

Changes in the Distribution of the α3 Na+/K+ ATPase Subunit in Heterozygous Lurcher Purkinje Cells as a Genetic Model of Chronic Depolarization during Development

1Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, P.O. Box 21247, Baltimore, MD 21228, USA
2Department of Biology, University of Maryland Baltimore County, Baltimore, MD 21201, USA
3Université Pierre et Marie Curie-P6, UMR7102, 75005 Paris, France
4Institut de la Longévité, Hôpital Charles Foix, 94205 Ivry-Sur-Seine, France

Received 9 October 2013; Revised 28 December 2013; Accepted 13 January 2014; Published 27 February 2014

Academic Editor: Alessio D’Alessio

Copyright © 2014 Rebecca McFarland et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A common assumption of excitotoxic mechanisms in the nervous system is that the ionic imbalance resulting from overstimulation of glutamate receptors and increased Na+ and Ca++ influx overwhelms cellular energy metabolic systems leading to cell death. The goal of this study was to examine how a chronic Na+ channel leak current in developing Purkinje cells in the heterozygous Lurcher mutant (+/Lc) affects the expression and distribution of the α3 subunit of the Na+/K+ ATPase pump, a key component of the homeostasis system that maintains ionic equilibrium in neurons. The expression pattern of the catalytic α3 Na+/K+ ATPase subunit was analyzed by immunohistochemistry, histochemistry, and Western Blots in wild type (WT) and +/Lc cerebella at postnatal days P10, P15, and P25 to determine if there are changes in the distribution of active Na+/K+ ATPase subunits in degenerating Purkinje cells. The results suggest that the expression of the catalytic α3 subunit is altered in chronically depolarized +/Lc Purkinje cells, although the density of active Na+/K+ ATPase pumps is not significantly altered compared with WT in the cerebellar cortex at P15, and then declines from P15 to P25 in the +/Lc cerebellum as the +/Lc Purkinje cells degenerate.