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Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/59523
Title: 1-Ethyl-2-benzimidazolinone (EBIO) suppresses epileptiform activity in in vitro hippocampus
Authors: Garduño, J.; Galván, E.; Fernández De Sevilla, D.; Buño, W.
Issue Date: 2005
Publisher: Pergamon Press
Citation: Neuropharmacology 49: 376- 388 (2005)
Abstract: Ca2+-activated K+ currents with medium (mI AHP) and slow (sIAHP) kinetics, that mediate the post-spike medium and slow after-hyperpolarization (AHP), respectively, play critical roles in regulating neuronal excitability and the spread of epileptiform activity and could provide new therapeutic targets for the management of epileptic patients. We tested if the enhancement of the mI AHP by 1-ethyl-2-benzimidazolinone (EBIO) could suppress epileptiform activity in two in vitro models of epileptogenesis induced in CA3 hippocampal pyramidal neurons by superfusion with 4-AP- and kainate-Mg2+-free solutions. Both interictal- and ictal-like epileptiform activities were reversibly suppressed by EBIO concentrations between 200 μM and 1 mM. EBIO predominantly acted by a strong reduction of excitability via an increase (≈450%) of the mIAHP, without changing the sIAHP. Glutamatergic excitatory synaptic transmission was also diminished (≈50%) by 1 mM EBIO. In contrast, EBIO concentrations <400 μM had no effect on synaptic excitation, consistent with a lesser sensitivity to the drug than the mIAHP. Apamine (100 nM), a toxin that specifically inhibits the mIAHP, rapidly and reversibly antagonized the blocking effects of EBIO on epileptiform activity. Our results suggest that manipulations that enhance the mIAHP may prove adequate in the treatment of epilepsies; they also suggest that an abnormal down regulation of the mIAHP may be a key factor in the genesis of hyperexcitable states. © 2005 Elsevier Ltd. All rights reserved.
URI: http://hdl.handle.net/10261/59523
Identifiers: doi: 10.1016/j.neuropharm.2005.03.021
issn: 0028-3908
DOI: 10.1016/j.neuropharm.2005.03.021
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