Changes in the Distribution of the α 3 Na(+)/K(+) ATPase Subunit in Heterozygous Lurcher Purkinje Cells as a Genetic Model of Chronic Depolarization during Development.
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 α 3 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 α 3 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 α 3 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.
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, P.O. Box 21247, Baltimore, MD 21228, USA ; Department of Biology, University of Maryland Baltimore County, Baltimore, MD 21201, USA.
Rebecca
0000-0003-0081-2677
R
McFarland
Université Pierre et Marie Curie-P6, UMR7102, 75005 Paris, France.
Hadi S
HS
Zanjani
Université Pierre et Marie Curie-P6, UMR7102, 75005 Paris, France ; Institut de la Longévité, Hôpital Charles Foix, 94205 Ivry-Sur-Seine, France.
Jean
J
Mariani
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, P.O. Box 21247, Baltimore, MD 21228, USA.
Michael W
MW
Vogel