Lowering of the potassium concentration induces epileptiform activity in guinea-pig hippocampal slices

Extra- and intracellular recording techniques were used to study the epilep tiform activity generated by guinea-pig hippocampal slices perfused with lo w potassium containing artificial cerebrospinal fluid. Extracellular field potentials were recorded in CA1 and CA3 regions along with intracellular re cordings in CA3 subfield. Reduction of the extracellular potassium concentr ation [K'](o) from 4 to 2 mM caused a transient neuronal hyperpolarisation which was followed by a repolarisation and subsequent depolarisation period . Paroxysmal depolarisation shifts occurred during the transient hyperpolar isation period while epileptic field potentials (EFP) appeared in the late repolarisation or early depolarisation phase. EFP elicited by reduction of [K+](o) were neither affected by blockade of N-methyl-D-aspartate (NMDA) gl utamate-subreceptor or gamma aminobutyric acid receptor, nor by application of the organic calcium channel blocker nifedipine or the anticonvulsant dr ugs carbamazepine and valproic acid. Upon application of non-NMDA glutamate -subreceptor blocker the EFP were abolished in all trials, while applicatio n of the organic calcium channel blocker verapamil only suppressed the EFP in some cases. The results point to a novel mechanism of epileptogenesis an d may provide an in vitro model for the development of new drugs against di fficult-to-treat epilepsy. (C) 2001 Elsevier Science B.V. All rights reserv ed.