Aims: 

We investigated the effect of the glutamate receptor antagonist pretreatment on neuronal activity and astrocytic swelling accompanying acute 4-AP convulsions; and the relation between connexin 43 (Cx43) phosphorylation and astrocytic swelling.

Methods: 

Male Wistar rats after GYKI 52466 or MK801 pretreatment received the convulsant 4-AP. The control groups received the solvent of antagonists and 4-AP. GYKI: 1 h after the 4-AP, brain samples were processed for c-fos and parvalbumin (PV) immunohistochemistry and electron microscopy (EM). MK801: 1, 3 and 24 h after 4-AP, brain samples were processed for RT-PCR, Western blot and EM.

Results: 

In the GYKI-pretreated groups, the latencies of GTCS increased; the GTCS occurrences decreased. The higher dose GYKI significantly decreased the number of double-labelled cells in the neocortex. In the hippocampus even the lower dose GYKI pretreatment caused significant reduction, in the number of the c-fos-IR and the double-labelled cells. Astrocytic swelling in the neocortexwas significantly increased, whereas in the hippocampus significantly decreased with lower dose of GYKI. MK801 significantly reduced the astrocytic swelling and prevented the Cx43 dephosphorylation. The astrocytic swelling, however, timely exceeded the Cx43 dephosphorylation, but after 3h, followed the reduction of dephosphorylation.

Conclusion: 

Our results suggest that rather the antagonists of the NMDA than AMPA receptors play crucial role in circumventing astrocytic swelling. The hippocampal activation was rather dependent on AMPA receptors. We propose a biphasic process of the astrocytic swelling: the early phase is characterised by Ca²⁺ and Na⁺ influx (increased extracellular glutamate), whereas in the late phase (after 3h) the opening of the gap junction hemichannels (Cx43 dephosphorylation) is more important.

Support: 

TÁMOP-4.2.1/B-09/1/KONV-2010-0005