Research reportEffects of standard anticonvulsant drugs on different patterns of epileptiform discharges induced by 4-aminopyridine in combined entorhinal cortex–hippocampal slices
Introduction
4-Aminopyridine (4-AP) is a convulsant which induces different types of seizure activity dependent on mode of application and area studied. 4-AP is well know to interfere with different types of K+ channels. These include D type [25] and A type K+ currents [27] and a subportion of delayed rectifier currents 12, 14. As a consequence, neuronal activity increases and bursting behaviour can be induced. Moreover, transmitter release is strongly augmented involving both inhibitory and excitatory neurotransmitters 20, 26.
4-AP induces different types of epileptiform discharges in combined entorhinal cortex (EC)–hippocampal slices. These areas are intimately involved in generation of drug resistant temporal lobe epilepsies. We therefore wanted to know how different conventional anticonvulsant affect the different patterns of epileptiform discharges in this area.
Previous studies have shown that in hippocampal areas CA3 and CA1 short recurrent discharges dominate [24] and that only rarely SLEs occur in adult transverse slices. In contrast, in the EC, SLEs regularly occur. These are characterized by long-lasting slow negative field potential shifts superimposed by initially high frequency low amplitude and later by low frequency electrographic activity. It was shown that such seizure like events are associated with ionic shifts comparable to those observed during SLEs in the intact animals [13]. Between SLEs interictal discharges occur which are also associated with rises in [K+] comparable to those observed during interictal discharges in the penicillin focus [10] and other focus models in intact animals. This is in contrast to the short recurrent discharges in the hippocampus which are often thought to represent interictal discharges. These are not associated with larger rises in [K+]. This suggests that generation mechanisms for the short recurrent discharges in the hippocampus and the interictal discharges in the EC are different. In fact it has been previously shown that interictal discharges can persist after blockade of glutamate receptors, but they are sensitive to bicuculline [1]. This suggests that GABAergic mechanisms are involved in generation of these events.
Section snippets
Tissue preparation
Deeply ether-anesthetised Wistar rats of both sexes (6–8 weeks, 180–250 g) were decapitated and the brain was removed and immersed in artificial cerebrospinal fluid (ACSF) at 4°C. The brain was hemisected, and horizontal slices (400 μm) containing temporal cortex area 2 or 3, perirhinal cortex, EC, the dentate gyrus, hippocampal areas CA1–4 and the subiculum were prepared as previously described [11]. The slices were transferred to an interface recording chamber and continuously perfused (1.6
Discussion
The present data indicate that application of 4-AP is able to induce different patterns of epileptiform activity with different pharmacological properties.
It has been proposed [21] that the NGPs are initiated by synchronous firing of inhibitory interneurons. Furthermore, it has been reported that in the presence of NBQX and APV the remaining NGPs are completely blocked by application of bicuculline [2]. This was confirmed by our experiments; remaining potentials after application of fast
Acknowledgements
C. Brückner is a recipient of a grant from Schering foundation. We thank Dr. A. Draguhn and Dr. D. Schmitz for helpful discussion and Drs H.-J. Gabriel and H. Siegmund for technical support.
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