Excitotoxic death of a subset of embryonic rat motor neurons in vitro

Hugh J.L. Fryer, Ronald J. Knox, Stephen M. Strittmatter, Robert G. Kalb*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

We have used cultures of purified embryonic rat spinal cord motor neurons to study the neurotoxic effects of prolonged ionotropic glutamate receptor activation. NMDA and non-NMDA glutamate receptor agonists kill a maximum of 40% of the motor neurons in a concentration- and time-dependent manner, which can be blocked by receptor subtype-specific antagonists. Subunit-specific antibodies stain all of the motor neurons with approximately the same intensity and for the same repertoire of subunits, suggesting that the survival of the nonvulnerable population is unlikely to be due to the lack of glutamate receptor expression. Extracellular Ca2+ is required for excitotoxicity, and the route of entry initiated by activation of non-NMDA, but not NMDA, receptors is L-type Ca2+ channels. Ca2+ imaging of motor neurons after application of specific glutamate receptor agonists reveals a sustained rise in intracellular Ca2+ that is present to a similar degree in most motor neurons, and can be blocked by appropriate receptor/channel antagonists. Although the lethal effects of glutamate receptor agonists are seen in only a subset of cultured motor neurons, the basis of this selectivity is unlikely to be simply the glutamate receptor phenotype or the level/pattern of rise in agonist-evoked intracellular Ca2+.

Original languageEnglish (US)
Pages (from-to)500-513
Number of pages14
JournalJournal of neurochemistry
Volume72
Issue number2
DOIs
StatePublished - 1999

Keywords

  • Ca imaging
  • Ca-dependent cell death
  • Cell culture
  • Excitotoxicity
  • Ionotropic glutamate receptors
  • L-type Ca channels
  • Motor neurons

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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