Entorhinal cortex is a highly
epilepsy-prone brain region. Effects of repetitive
seizures on
ionotropic glutamate receptors (iGluRs) were investigated in rat entorhinal cortex slices.
Seizures were induced by daily administration of
4-aminopyridine (4-AP). Electrophysiological, pharmacological and histological investigations were carried out to determine changes in synaptic efficacy and in sensitivity of iGluRs due to recurring
seizures. Repeated 4-AP-induced
seizures increased the amplitude of evoked synaptic field responses in rat entorhinal cortical slices. While vulnerability to inhibition of
AMPA receptors by the specific antagonist
GYKI 52466 was slightly reduced, responsiveness to
NMDA receptor antagonist APV remained unaffected. Testing of bivalent
cation permeability of iGluRs revealed reduced Ca(2+)-influx through non-
NMDA receptors. According to the semi-quantitative histoblot analysis GluA1-4, GluA1, GluA2, GluK5, GluN1 and GluN2A
subunit protein expression differently altered. While there was a marked decrease in the level of GluA1-4, GluA2 and
GluK5 receptor subunits, GluA1 and GluN2A
protein levels moderately increased. The results indicate that brief convulsions, repeated daily for 10 days can increase overall entorhinal cortex excitability despite a reduction in
AMPA/
kainate receptor activity, probably through the alteration of local network susceptibility.