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.
Department of Neurology, Medical College of Virginia, Richmond 23298-0599.
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S
Sombati
D A
DA
Coulter
R J
RJ
DeLorenzo
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004594:Electrophysiology / Q000379:methods; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D006624:Hippocampus / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000502:physiology
D005971:Glutamates; D009498:Neurotoxins; D011810:Quinoxalines; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate