The effects of potassium-induced depolarization, glutamate receptor antagonists and N-methyl-D-aspartate on neuronal survival in cultured neocortex explants.
The effects of elevating the potassium concentration of the growth medium of neocortical explants was studied. Under control conditions, 10 mM potassium resulted in ca 20% decrease in the number of surviving neurons. The same potassium concentration, however, was clearly neurotrophic in tetrodotoxin-grown cultures: tetrodotoxin-induced neuronal death was significantly reduced. Both effects could be mimicked by the addition of 10 microM N-methyl-D-aspartate (NMDA); lower concentrations were without effect; higher concentrations were neurotoxic under both control and tetrodotoxin conditions. The neurotoxic, as well as the neurotrophic effects of 10 mM potassium appear to be mediated through depolarization-induced glutamate release since they could be influenced by the application of glutamate receptor antagonists. The addition of the NMDA receptor antagonist D-2-amino-7-phosphonoheptanoate (APH) blocked the trophic effect of 10 mM potassium in tetrodotoxin-grown cultures, resulting in low survival. On the other hand, the addition of the non-NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) resulted in neuronal survival similar to control cultures, indicating that it blocked the toxic effects of glutamate, leaving the trophic effects on the NMDA receptor untouched. Under control (non-TTX) conditions, neither DNQX nor APH showed significant effects on 10 mM potassium-induced cell death, indicating that stimulation of the non-NMDA, as well as the NMDA receptors is neurotoxic. This differential effect of NMDA receptor stimulation on neuronal survival is discussed with respect to the maturational and/or functional state of the neurons in the culture.
Ruijter
J M
JM
Netherlands Institute for Brain Research, Amsterdam.
Baker
R E
RE
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology*; D046508:Culture Techniques; D004594:Electrophysiology; D005971:Glutamates / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors*; D013779:Tetrodotoxin / Q000494:pharmacology
D000596:Amino Acids; D005971:Glutamates; D011810:Quinoxalines; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D013779:Tetrodotoxin; C056723:FG 9041; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid; D011188:Potassium