Novel approach to studying N‐methyl‐D‐aspartate receptor function in the kindling model of epilepsy

Kindling is the most widely studied animal model of epilepsy. This manuscript reviews studies of the role of N‐methyl‐D‐aspartate (NMDA) receptors in the kindling model. Pharmacologic studies suggest that 1) NMDA receptor activation contributes to the development of kindling; and 2) kindled seizures may be due in part to enhanced activation of NMDA receptors. Electrophysiologic studies demonstrate that NMDA receptors participate in synaptic activation of hippocampal dentate granule cells of kindled but not control animals. Biochemical studies demonstrate an enhanced sensitivity of kindled hippocampal slices to NMDA. Raising the possibility of enhanced function of the NMDA receptor channel complex itself. Radiohistochemical studies disclose no increase in affinity or number of NMDA receptors. Major emphasis is placed on development of a novel approach to study NMDA receptor function in isolated membrances, namely NMDA control of radiolabeled uncompetitive antagonist binding to a site presumably within the NMDA channel. Application of this novel approach will permit examination of NMDA and glycine receptor function and their control by zinc in the kindling model. Copyright © 1989 Alan R. Liss, Inc.

Duke Scholars

Author James O'Connell McNamara Sr. Neurobiology

Author J. Victor Nadler Pharmacology & Cancer Biology