title: Differential sensitivity to induction of spreading depression by partial disinhibition in chronically epileptic human and rat as compared to native rat neocortical tissue.
abstract: Spreading depression (SD) is characterized by a transient breakdown of neuronal function concomitant with a massive failure of ion homeostasis. It is a phenomenon that can be induced in neocortical tissue by raising excitability, e.g. injection of K(+), application of glutamatergic agonists, or blocking Na(+)/K(+) ATPase. Here we report a novel method of SD induction using minimal disinhibition with application of low concentrations (5 microM) of the GABA(A) receptor blocker bicuculline. This procedure-while subthreshold for epileptiform activity-readily induced spontaneous SDs in native rat neocortical slices, accompanied by typical depolarizations of neurons and glial cells. In contrast, in human neocortical preparations obtained from epilepsy surgery, in approximately 20% of the slices spontaneous epileptiform activity appeared with this bicuculline dosage without SDs. Raising the concentration of bicuculline to an epileptogenic dose (10 microM) in human tissue also resulted in the generation of epileptiform activity only. Likewise, in slices from pilocarpine-treated, chronically epileptic rats, bicuculline also only induced epileptiform activity without eliciting SDs. The experiments indicate that chronic epilepsy causes a differential sensitivity to partial GABA(A) receptor blockade with regard to induction of SD.
authors.affiliation: Institute of Physiology, University of Münster, Robert-Koch-Str. 27a, 48149 Münster, Germany. ruediger.koehling@ukb.uni-bonn.de
authors.forename: R
authors.initials: R
authors.lastname: Köhling
authors.forename: U R
authors.initials: UR
authors.lastname: Koch
authors.forename: G
authors.initials: G
authors.lastname: Hagemann
authors.forename: C
authors.initials: C
authors.lastname: Redecker
authors.forename: H
authors.initials: H
authors.lastname: Straub
authors.forename: E-J
authors.initials: EJ
authors.lastname: Speckmann
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002908:Chronic Disease; D013181:Cortical Spreading Depression / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D018756:GABA Antagonists / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D019579:Neocortex / Q000502:physiology*; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010277:Parasympathomimetics / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
chemical_list: D018756:GABA Antagonists; D010277:Parasympathomimetics; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D010862:Pilocarpine; D015763:2-Amino-5-phosphonovalerate; D001640:Bicuculline