title: Lowering of the potassium concentration induces epileptiform activity in guinea-pig hippocampal slices.
abstract: Extra- and intracellular recording techniques were used to study the epileptiform activity generated by guinea-pig hippocampal slices perfused with low potassium containing artificial cerebrospinal fluid. Extracellular field potentials were recorded in CA1 and CA3 regions along with intracellular recordings in CA3 subfield. Reduction of the extracellular potassium concentration [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 hyperpolarisation 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) glutamate-subreceptor or gamma aminobutyric acid receptor, nor by application of the organic calcium channel blocker nifedipine or the anticonvulsant drugs carbamazepine and valproic acid. Upon application of non-NMDA glutamate-subreceptor blocker the EFP were abolished in all trials, while application of the organic calcium channel blocker verapamil only suppressed the EFP in some cases. The results point to a novel mechanism of epileptogenesis and may provide an in vitro model for the development of new drugs against difficult-to-treat epilepsy.
authors.affiliation: Institut für Physiologie, Universität Münster, Robert-Koch-Strasse 27a, D-48149 Münster, Germany.gorjial@uni-muenster.de
authors.forename: A
authors.initials: A
authors.lastname: Gorji
authors.forename: M
authors.initials: M
authors.lastname: Madeja
authors.forename: H
authors.initials: H
authors.lastname: Straub
authors.forename: R
authors.initials: R
authors.lastname: Köhling
authors.forename: E J
authors.initials: EJ
authors.lastname: Speckmann
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D004827:Epilepsy / Q000378:metabolism* / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D018756:GABA Antagonists / Q000494:pharmacology; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D011188:Potassium / Q000378:metabolism*; D011191:Potassium Deficiency / Q000378:metabolism* / Q000503:physiopathology; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D011188:Potassium