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. 1986 Nov;380:175–189. doi: 10.1113/jphysiol.1986.sp016279

Involvement of N-methyl-D-aspartate receptors in epileptiform bursting in the rat hippocampal slice.

R Dingledine, M A Hynes, G L King
PMCID: PMC1182931  PMID: 2886653

Abstract

The effects of the N-methyl-D-aspartate (NMDA) receptor antagonist, D-2-amino-5-phosphonovaleric acid (D-APV), and other excitatory amino acid antagonists, were studied on CA1 pyramidal neurones treated with picrotoxin or bicuculline to reduce synaptic inhibition mediated by gamma-aminobutyric acid (GABA). Under these conditions epileptiform burst firing is readily produced by orthodromic stimulation of the pyramidal cell population. D-APV reduced the plateau amplitude and duration of the depolarization underlying evoked and spontaneous bursts without affecting membrane potential, input resistance or the ability of the cell to fire a Ca2+ spike or a short train of Na+ spikes. A late component of the subthreshold excitatory post-synaptic potential (e.p.s.p.) was voltage dependent, being reduced in amplitude on membrane hyperpolarization. D-APV selectively removed this component of the e.p.s.p. in disinhibited slices. In contrast, in the absence of GABA antagonists, D-APV had no noticeable effect on the e.p.s.p. as studied with field potential recordings. The concentration-response relationship of the inhibitory effect of D-APV and L-APV on population spike bursts was studied. The action of APV was highly stereoselective; the EC50 of D-APV was approximately 700 nM, whereas a similar inhibition required 540 microM-L-APV. A number of other excitatory amino acid antagonists were tested at a fixed concentration (100 microM). Among them, the quisqualate antagonist gamma-D-glutamylaminomethyl sulphonic acid was ineffective against epileptiform bursts. In the low nanomolar concentration range both D- and L-APV potentiated bursting. These results suggest that in the absence of GABAergic inhibition, a significant component of the slow depolarization underlying burst firing is voltage dependent, synaptic in origin and mediated by NMDA receptors. We propose that, under normal (non-epileptic) physiological conditions, the balance between synaptic inhibition mediated by GABA receptors and synaptic excitation mediated by NMDA receptors may modulate the excitability of pyramidal cell dendrites.

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Selected References

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