Kindling reduces sensitivity of CA3 hippocampal pyramidal cells to competitive NMDA receptor antagonists

Kindling is a form of experimental epilepsy in which periodic electrical stimulation of a brain pathway induces a permanently hyperexcitable state. A previous study demonstrated that kindling enhances the sensitivity of hippocampal CA3 pyramidal cells to NMDA (N-methyl-D-aspartate), consistent with a greater expression of NMDA receptors. We have tested the possibility that kindling also changes the sensitivity of these neurons to competitive NMDA receptor antagonists. When depolarizing responses to NMDA were studied with a grease-gap preparation 1-5 months after the last evoked seizure, higher concentrations of competitive antagonist were required to reduce response amplitudes. Schild analysis yielded higher KD values for all three antagonists tested. This finding suggests that kindling provokes the expression by CA3 pyramidal cells of NMDA receptors with reduced affinity for competitive antagonists.