These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Involvement of N-methyl-D-aspartate receptors in epileptiform bursting in the rat hippocampal slice.
    Author: Dingledine R, Hynes MA, King GL.
    Journal: J Physiol; 1986 Nov; 380():175-89. PubMed ID: 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.
    [Abstract] [Full Text] [Related] [New Search]