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

Abstract

A rescue window for glutamate-insulted cells with regard to Ca 2+ 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 Ca 2+ influx up to 5 min after the insult determined the fate of cells. But we also demonstrated that the elevated intracellular Ca 2+ did not always induce neurotoxicity. High concentration of potassium chloride plus FPL64176, an agonist of L-type Ca 2+ channels did not induce neuronal cell death, even though their combination elicited equal elevation of intracellular Ca 2+ to that by toxic concentration of glutamate, demonstrating that locally elevated intracellular Ca 2+ around NMDA receptors is important in the induction of neuronal cell death.