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GABA(B) receptor outward currents are transiently disclosed by the convulsant 4-aminopyridine in vitro

The K(+) channel blocker 4-aminopyridine (4AP) has been extensively used to investigate the mechanisms underlying neuronal network synchronization in both in vitro and in vivo animal models of focal epilepsy. 4AP-induced effects are paralleled by an increase in both excitatory and inhibitory neurotr...

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Autores principales: Cattani, Adriano, Wang, Siyan, Lévesque, Maxime, Farmer, Jean-Pierre, Dudley, Roy William Roland, Avoli, Massimo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663127/
https://www.ncbi.nlm.nih.gov/pubmed/38020804
http://dx.doi.org/10.1016/j.crneur.2023.100117
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author Cattani, Adriano
Wang, Siyan
Lévesque, Maxime
Farmer, Jean-Pierre
Dudley, Roy William Roland
Avoli, Massimo
author_facet Cattani, Adriano
Wang, Siyan
Lévesque, Maxime
Farmer, Jean-Pierre
Dudley, Roy William Roland
Avoli, Massimo
author_sort Cattani, Adriano
collection PubMed
description The K(+) channel blocker 4-aminopyridine (4AP) has been extensively used to investigate the mechanisms underlying neuronal network synchronization in both in vitro and in vivo animal models of focal epilepsy. 4AP-induced effects are paralleled by an increase in both excitatory and inhibitory neurotransmitter release, but the mechanisms of action of 4AP on neuronal networks remain unclear. By employing simultaneous whole-cell patch clamp and field potential recordings from hippocampal CA3/4 pyramidal layer of acute brain slices obtained from mice (n = 30), we found that the appearance of epileptiform discharges induced by 4AP (100 μM) is consistently preceded by the transient recurrence of presumptive GABA(B) outward currents, which are not mirrored by any field activity. These GABA(B) outward currents still occurred during application of ionotropic glutamatergic antagonists (n = 12 cells) but were blocked by the GABA(B) receptor antagonist CGP55845 (n = 7). Our findings show that the transient occurrence of distinct GABA(B) outward currents precedes the appearance of 4AP-induced neuronal network synchronization leading to epileptiform activity in the rodent hippocampus in vitro.
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spelling pubmed-106631272023-11-17 GABA(B) receptor outward currents are transiently disclosed by the convulsant 4-aminopyridine in vitro Cattani, Adriano Wang, Siyan Lévesque, Maxime Farmer, Jean-Pierre Dudley, Roy William Roland Avoli, Massimo Curr Res Neurobiol Research Article The K(+) channel blocker 4-aminopyridine (4AP) has been extensively used to investigate the mechanisms underlying neuronal network synchronization in both in vitro and in vivo animal models of focal epilepsy. 4AP-induced effects are paralleled by an increase in both excitatory and inhibitory neurotransmitter release, but the mechanisms of action of 4AP on neuronal networks remain unclear. By employing simultaneous whole-cell patch clamp and field potential recordings from hippocampal CA3/4 pyramidal layer of acute brain slices obtained from mice (n = 30), we found that the appearance of epileptiform discharges induced by 4AP (100 μM) is consistently preceded by the transient recurrence of presumptive GABA(B) outward currents, which are not mirrored by any field activity. These GABA(B) outward currents still occurred during application of ionotropic glutamatergic antagonists (n = 12 cells) but were blocked by the GABA(B) receptor antagonist CGP55845 (n = 7). Our findings show that the transient occurrence of distinct GABA(B) outward currents precedes the appearance of 4AP-induced neuronal network synchronization leading to epileptiform activity in the rodent hippocampus in vitro. Elsevier 2023-11-17 /pmc/articles/PMC10663127/ /pubmed/38020804 http://dx.doi.org/10.1016/j.crneur.2023.100117 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Cattani, Adriano
Wang, Siyan
Lévesque, Maxime
Farmer, Jean-Pierre
Dudley, Roy William Roland
Avoli, Massimo
GABA(B) receptor outward currents are transiently disclosed by the convulsant 4-aminopyridine in vitro
title GABA(B) receptor outward currents are transiently disclosed by the convulsant 4-aminopyridine in vitro
title_full GABA(B) receptor outward currents are transiently disclosed by the convulsant 4-aminopyridine in vitro
title_fullStr GABA(B) receptor outward currents are transiently disclosed by the convulsant 4-aminopyridine in vitro
title_full_unstemmed GABA(B) receptor outward currents are transiently disclosed by the convulsant 4-aminopyridine in vitro
title_short GABA(B) receptor outward currents are transiently disclosed by the convulsant 4-aminopyridine in vitro
title_sort gaba(b) receptor outward currents are transiently disclosed by the convulsant 4-aminopyridine in vitro
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663127/
https://www.ncbi.nlm.nih.gov/pubmed/38020804
http://dx.doi.org/10.1016/j.crneur.2023.100117
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