title: Astrocytes modulate neural network activity by Ca²+-dependent uptake of extracellular K+.
abstract: Astrocytes are electrically nonexcitable cells that display increases in cytosolic calcium ion (Ca²+) in response to various neurotransmitters and neuromodulators. However, the physiological role of astrocytic Ca²+ signaling remains controversial. We show here that astrocytic Ca²+ signaling ex vivo and in vivo stimulated the Na+,K+-ATPase (Na+- and K+-dependent adenosine triphosphatase), leading to a transient decrease in the extracellular potassium ion (K+) concentration. This in turn led to neuronal hyperpolarization and suppressed baseline excitatory synaptic activity, detected as a reduced frequency of excitatory postsynaptic currents. Synaptic failures decreased in parallel, leading to an increase in synaptic fidelity. The net result was that astrocytes, through active uptake of K+, improved the signal-to-noise ratio of synaptic transmission. Active control of the extracellular K+ concentration thus provides astrocytes with a simple yet powerful mechanism to rapidly modulate network activity.
authors.affiliation: Division of Glia Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical School, Rochester, NY 14640, USA.
authors.forename: Fushun
authors.initials: F
authors.lastname: Wang
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Smith
authors.forename: Qiwu
authors.initials: Q
authors.lastname: Xu
authors.forename: Takumi
authors.initials: T
authors.lastname: Fujita
authors.forename: Akemichi
authors.initials: A
authors.lastname: Baba
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsuda
authors.forename: Takahiro
authors.initials: T
authors.lastname: Takano
authors.forename: Lane
authors.initials: L
authors.lastname: Bekar
authors.forename: Maiken
authors.initials: M
authors.lastname: Nedergaard
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009415:Nerve Net / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000502:physiology; D012414:Rubidium Radioisotopes / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D043562:Receptors, G-Protein-Coupled; D012414:Rubidium Radioisotopes; D010042:Ouabain; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D002118:Calcium