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

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 chro...

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Main Authors: Rebecca McFarland, Hadi S. Zanjani, Jean Mariani, Michael W. Vogel
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:International Journal of Cell Biology
Online Access:http://dx.doi.org/10.1155/2014/152645
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author Rebecca McFarland
Hadi S. Zanjani
Jean Mariani
Michael W. Vogel
author_facet Rebecca McFarland
Hadi S. Zanjani
Jean Mariani
Michael W. Vogel
author_sort Rebecca McFarland
collection DOAJ
description 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.
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spelling doaj-art-e5e5ebedff8641b087b653ee1a7f46622025-08-20T03:26:04ZengWileyInternational Journal of Cell Biology1687-88761687-88842014-01-01201410.1155/2014/152645152645Changes in the Distribution of the α3 Na+/K+ ATPase Subunit in Heterozygous Lurcher Purkinje Cells as a Genetic Model of Chronic Depolarization during DevelopmentRebecca McFarland0Hadi S. Zanjani1Jean Mariani2Michael W. Vogel3Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, P.O. Box 21247, Baltimore, MD 21228, USAUniversité Pierre et Marie Curie-P6, UMR7102, 75005 Paris, FranceUniversité Pierre et Marie Curie-P6, UMR7102, 75005 Paris, FranceMaryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, P.O. Box 21247, Baltimore, MD 21228, USAA 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.http://dx.doi.org/10.1155/2014/152645
spellingShingle Rebecca McFarland
Hadi S. Zanjani
Jean Mariani
Michael W. Vogel
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
International Journal of Cell Biology
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url http://dx.doi.org/10.1155/2014/152645
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