title: The neuroglial potassium cycle during neurotransmission: role of Kir4.1 channels.
abstract: 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 Kir4.1 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 Kir4.1 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 Kir4.1 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 Kir4.1 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 Kir4.1 channels are crucially involved in extracellular potassium homeostasis regulating theta rhythmic activity.
authors.affiliation: Neuroglial Interactions in Cerebral Physiopathology, Center for Interdisciplinary Research in Biology, Collège de France, INSERM U1050, CNRS UMR 7241, Labex Memolife, PSL Research University, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Sibille
authors.affiliation: IBENS, Ecole Normale Supérieure, INSERM U1024, CNRS UMR 8197, Paris, France; Université Paris 6, Paris, France.
authors.forename: Khanh
authors.initials: K
authors.lastname: Dao Duc
authors.affiliation: IBENS, Ecole Normale Supérieure, INSERM U1024, CNRS UMR 8197, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Holcman
authors.affiliation: Neuroglial Interactions in Cerebral Physiopathology, Center for Interdisciplinary Research in Biology, Collège de France, INSERM U1050, CNRS UMR 7241, Labex Memolife, PSL Research University, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rouach
mesh_terms: D000200:Action Potentials; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008959:Models, Neurological; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D000098854:Kcnj10 Channel
chemical_list: D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D011188:Potassium
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