Seizure-like discharges were observed in slices of human epileptogenic neocortex maintained in vitro when [Mg2+]o was lowered near to zero. This type of epileptiform activity: (1) could occur spontaneously or following extracellular focal stimuli; (2) resembled the electrographic pattern associated with tonic-clonic seizures; (3) was accompanied by increases in [K+]o (maximally 6.2 mM from a baseline of 3.25 mM) and decreases in [Ca2+]o (maximally 0.23 mM from a baseline of 1.8 mM). Application of the selective antagonist of N-methyl-D-aspartate (NMDA) receptors, DL-2-amino-5-phosphonovalerate, suppressed in a reversible manner both spontaneous and stimulus-induced seizure-like discharges, suggesting that NMDA-activated conductances are important for the genesis of prolonged epileptiform discharges generated by human epileptogenic neocortical slices.
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