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

We have used cultures of purified embryonic rat spinal cord motor neurons t o study the neurotoxic effects of prolonged ionotropic glutamate receptor a ctivation. NMDA and non-NMDA glutamate receptor agonists kill a maximum of 40% of the motor neurons in a concentration- and time-dependent manner, whi ch can be blocked by receptor subtype-specific antagonists. Subunit-specifi c antibodies stain all of the motor neurons with approximately the same int ensity and for the same repertoire of subunits, suggesting that the surviva l of the nonvulnerable population is unlikely to be due to the lack of glut amate receptor expression. Extracellular Ca2+ is required for excitotoxicit y, 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 ap plication of specific glutamate receptor agonists reveals a sustained rise in intracellular Ca2+ that is present to a similar degree in most motor neu rons, and can be blocked by appropriate receptor/channel antagonists. Altho ugh the lethal effects of glutamate receptor agonists are seen in only a su bset of cultured motor neurons, the basis of this selectivity is unlikely t o be simply the glutamate receptor phenotype or the level/pattern of rise i n agonist-evoked intracellular Ca2+.