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

J Neurochem. 1999 Feb;72(2):500-13. doi: 10.1046/j.1471-4159.1999.0720500.x.

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+.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Animals
  • Calcium / metabolism
  • Calcium Channels / physiology
  • Calcium Channels, L-Type
  • Cell Culture Techniques / methods
  • Cell Death / drug effects
  • Cells, Cultured
  • Dizocilpine Maleate / pharmacology
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • Glutamic Acid / pharmacology
  • Glutamine / toxicity
  • Glycine / pharmacology
  • Kainic Acid / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Motor Neurons / chemistry*
  • Motor Neurons / cytology*
  • Motor Neurons / metabolism
  • N-Methylaspartate / pharmacology
  • Nerve Tissue Proteins / physiology
  • Neurotoxins / toxicity*
  • Potassium / pharmacology
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / physiology
  • Receptors, Kainic Acid / physiology
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Spinal Cord / cytology
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology

Substances

  • Calcium Channels
  • Calcium Channels, L-Type
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Nerve Tissue Proteins
  • Neurotoxins
  • Receptors, AMPA
  • Receptors, Kainic Acid
  • Receptors, N-Methyl-D-Aspartate
  • Glutamine
  • Glutamic Acid
  • N-Methylaspartate
  • Dizocilpine Maleate
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Potassium
  • Kainic Acid
  • Calcium
  • Glycine