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The Neuroglial Potassium Cycle during Neurotransmission: Role of Kir4.1 Channels

Neuronal excitability relies on inward sodium and outward potassium fluxes during action potentials. To prevent neuronal hyperexcitability, potassium ions have to be taken up quickly. However, the dynamics of the activity-dependent potassium fluxes and the molecular pathways underlying extracellular...

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Autores principales: Sibille, Jérémie, Dao Duc, Khanh, Holcman, David, Rouach, Nathalie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380507/
https://www.ncbi.nlm.nih.gov/pubmed/25826753
http://dx.doi.org/10.1371/journal.pcbi.1004137
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author Sibille, Jérémie
Dao Duc, Khanh
Holcman, David
Rouach, Nathalie
author_facet Sibille, Jérémie
Dao Duc, Khanh
Holcman, David
Rouach, Nathalie
author_sort Sibille, Jérémie
collection PubMed
description Neuronal excitability relies on inward sodium and outward potassium fluxes during action potentials. To prevent neuronal hyperexcitability, potassium ions have to be taken up quickly. However, the dynamics of the activity-dependent potassium fluxes and the molecular pathways underlying extracellular potassium homeostasis remain elusive. To decipher the specific and acute contribution of astroglial K(ir)4.1 channels in controlling potassium homeostasis and the moment to moment neurotransmission, we built a tri-compartment model accounting for potassium dynamics between neurons, astrocytes and the extracellular space. We here demonstrate that astroglial K(ir)4.1 channels are sufficient to account for the slow membrane depolarization of hippocampal astrocytes and crucially contribute to extracellular potassium clearance during basal and high activity. By quantifying the dynamics of potassium levels in neuron-glia-extracellular space compartments, we show that astrocytes buffer within 6 to 9 seconds more than 80% of the potassium released by neurons in response to basal, repetitive and tetanic stimulations. Astroglial K(ir)4.1 channels directly lead to recovery of basal extracellular potassium levels and neuronal excitability, especially during repetitive stimulation, thereby preventing the generation of epileptiform activity. Remarkably, we also show that K(ir)4.1 channels strongly regulate neuronal excitability for slow 3 to 10 Hz rhythmic activity resulting from probabilistic firing activity induced by sub-firing stimulation coupled to Brownian noise. Altogether, these data suggest that astroglial K(ir)4.1 channels are crucially involved in extracellular potassium homeostasis regulating theta rhythmic activity.
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spelling pubmed-43805072015-04-09 The Neuroglial Potassium Cycle during Neurotransmission: Role of Kir4.1 Channels Sibille, Jérémie Dao Duc, Khanh Holcman, David Rouach, Nathalie PLoS Comput Biol Research Article Neuronal excitability relies on inward sodium and outward potassium fluxes during action potentials. To prevent neuronal hyperexcitability, potassium ions have to be taken up quickly. However, the dynamics of the activity-dependent potassium fluxes and the molecular pathways underlying extracellular potassium homeostasis remain elusive. To decipher the specific and acute contribution of astroglial K(ir)4.1 channels in controlling potassium homeostasis and the moment to moment neurotransmission, we built a tri-compartment model accounting for potassium dynamics between neurons, astrocytes and the extracellular space. We here demonstrate that astroglial K(ir)4.1 channels are sufficient to account for the slow membrane depolarization of hippocampal astrocytes and crucially contribute to extracellular potassium clearance during basal and high activity. By quantifying the dynamics of potassium levels in neuron-glia-extracellular space compartments, we show that astrocytes buffer within 6 to 9 seconds more than 80% of the potassium released by neurons in response to basal, repetitive and tetanic stimulations. Astroglial K(ir)4.1 channels directly lead to recovery of basal extracellular potassium levels and neuronal excitability, especially during repetitive stimulation, thereby preventing the generation of epileptiform activity. Remarkably, we also show that K(ir)4.1 channels strongly regulate neuronal excitability for slow 3 to 10 Hz rhythmic activity resulting from probabilistic firing activity induced by sub-firing stimulation coupled to Brownian noise. Altogether, these data suggest that astroglial K(ir)4.1 channels are crucially involved in extracellular potassium homeostasis regulating theta rhythmic activity. Public Library of Science 2015-03-31 /pmc/articles/PMC4380507/ /pubmed/25826753 http://dx.doi.org/10.1371/journal.pcbi.1004137 Text en © 2015 Sibille et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Sibille, Jérémie
Dao Duc, Khanh
Holcman, David
Rouach, Nathalie
The Neuroglial Potassium Cycle during Neurotransmission: Role of Kir4.1 Channels
title The Neuroglial Potassium Cycle during Neurotransmission: Role of Kir4.1 Channels
title_full The Neuroglial Potassium Cycle during Neurotransmission: Role of Kir4.1 Channels
title_fullStr The Neuroglial Potassium Cycle during Neurotransmission: Role of Kir4.1 Channels
title_full_unstemmed The Neuroglial Potassium Cycle during Neurotransmission: Role of Kir4.1 Channels
title_short The Neuroglial Potassium Cycle during Neurotransmission: Role of Kir4.1 Channels
title_sort neuroglial potassium cycle during neurotransmission: role of kir4.1 channels
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380507/
https://www.ncbi.nlm.nih.gov/pubmed/25826753
http://dx.doi.org/10.1371/journal.pcbi.1004137
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