Glutamate up-regulates α1 and α2 subunits of the sodium pump in astrocytes of mixed telencephalic cultures but not in pure astrocyte cultures

Michael L. Brines, Richard J. Robbins

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Prior work employing an in vitro model of the cerebral cortex has shown that sodium pump activity is a critical determinant for neuronal survival of glutamate stimulation. We have hypothesized that up-regulation of total brain sodium pump activity will protect against potential excitotoxins. Increased sodium pump activity could theoretically occur by changes in the reaction rate (short-term) and/or by increased levels of sodium pump protein (long-term) and is potentially complex since the three catalytic (a) subunit isoforms of the sodium pump are distributed in a highly variable, cell-specific pattern in the brain. Short-term regulation (seconds to minutes) has been well studied: brain sodium pump exhibits a large dynamic range. In contrast, the possibility of long-term modulation of sodium pump activity has not been extensively explored. We used isoform specific antibodies and [3H]ouabain binding to determine whether prolonged stimulation of sodium pump activity in rodent telencephalic cultures increased total sodium pump enzyme. Exposure of mixed neuronal-glial cultures to high levels of glutamate (10 mM) for 18 h, which is highly toxic to neurons, was associated with an ≈ 80% increase in α1 and α2 subunit expression by glia. Induction of α2 subunit immunoreactivity was also associated with comparable changes in [3H]ouabain binding, suggesting that the up-regulation corresponded to functional α2 protein. Shorter (30 min) glutamate treatments, which also killed neurons, did not produce similar changes in sodium pump expression. In contrast to mixed cultures, pure astrocyte cultures had undetectable α2 and α3 and moderate levels of α1 protein, as confirmed by low levels of [3H]ouabain binding. Glutamate treatment using this protocol was associated with a decrease in α1 sodium pump expression. We conclude that long-term regulation of the sodium pump can be demonstrated in glia which have developed in the presence of neurons. Both α1 and α2 isoforms of the sodium pump are involved in this response to glutamate.

Original languageEnglish (US)
Pages (from-to)12-21
Number of pages10
JournalBrain Research
Volume631
Issue number1
DOIs
StatePublished - Dec 17 1993

Keywords

  • Excitotoxicity
  • Glia
  • Glutamate
  • Na,K-ATPase
  • Regulation
  • Sodium pump
  • Telencephalic culture

ASJC Scopus subject areas

  • Neuroscience(all)

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