NEUROTOXIC ACTIVATION OF GLUTAMATE RECEPTORS INDUCES AN EXTENDED NEURONAL DEPOLARIZATION IN CULTURED HIPPOCAMPAL-NEURONS

Intracellular recording revealed that cytotoxic activation of excitatory amino acid receptors by glutamate or N-methyl-D-aspartate (NMDA) elicited an extended neuronal depolarization (END) of at least 5 h duration following washout of glutamate in hippocampal neurons in culture. During END, cells were still responsive to glutamate, and still able to fire sodium spikes. END induction could be blocked by concurrent application of D-2-amino-5-phosphonovalerate (APV) or MK-801, but not 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), during the glutamate exposure. The induction of END by excitotoxic glutamate receptor activation may play a role in the pathophysiology of glutamate toxicity.