A narrow window for rescuing cells by the inhibition of calcium influx and the importance of influx route in rat cortical neuronal cell death induced by glutamate

A rescue window for glutamate-insulted cells with regard to Ca2+ influx was first investigated. The addition of EGTA, an impermeable calcium chelator to the culture within 5 min after the beginning of glutamate stimulation potently suppressed the neuronal cell death examined at 22 h. The effect of EGTA on rescuing cells decreased with the time delay of its addition to the system. MK-801, an antagonist of N-methyl-(D)-asparate (NMDA) receptor channels also inhibited the neuronal cell death in a similar manner to EGTA, suggesting Ca2+ influx up to 5 min after the insult determined the fate of cells. But we also demonstrated that the elevated intracellular Ca2+ did not always induce neurotoxicity, High concentration of potassium chloride plus FPL64176, an agonist of L-type Ca2+ channels did not induce neuronal cell death, even though their combination elicited equal elevation of intracellular Ca2+ to that by toxic concentration of glutamate, demonstrating that locally elevated intracellular Ca2+ around NMDA receptors is important in the induction of neuronal cell death. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.