Systemic administration of the
potassium channel blocker 4-aminopyridine (4-AP) elicits acute convulsions. Synchronized tonic-clonic activity develops during the first hour after the treatment. However, subsequent chronic spontaneous
seizures do not appear which suggests changes in neuronal excitability. The aim of our present work was to evaluate alterations in the glutamatergic transmission in the somatosensory cortex of rats following daily, brief convulsions elicited by 4-AP treatment. Changes in general neuronal excitability and pharmacological sensitivity of
glutamate receptors were tested in ex vivo electrophysiological experiments on brain slices. In parallel studies quantitative changes in subunit composition of
glutamate receptors were determined with immunohistoblot technique, together with the analysis of
kainate induced Co2+ uptake. The results of our coordinated electrophysiological, receptor-pharmacological and histoblot studies demonstrated that repeated, daily, short convulsions resulted in a significant decrease of the general excitability of the somatosensory cortex together with changes in
ionotropic glutamate receptor subunits. The relative inhibitory effect of the
AMPA receptor antagonist, however, did not change. The
NMDA receptor antagonist exerted somewhat stronger effect in the slices from convulsing animals. 4-AP pretreatment resulted in the attenuation of
kainate induced Co2+ uptake, which suggests either reduction in non-
NMDA receptors numbers or reduction in their Ca2+ permeability. Repeated
seizures decreased GluR1-4
AMPA receptor subunit levels in all cortical layers with a relaitve increase in GluR1 subunits. While the principle
NR1 NMDA receptor subunit showed no significant change, the staining density of NR2A subunit increased. These changes in
ionotropic glutamate receptors are consistent with reduced excitability at glutamatergic synapses following repeated 4-AP induced
seizures.