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Sci. Signal., 3 April 2012
Vol. 5, Issue 218, p. ra26
[DOI: 10.1126/scisignal.2002334]

RESEARCH ARTICLES

Astrocytes Modulate Neural Network Activity by Ca2+-Dependent Uptake of Extracellular K+

Fushun Wang1*, Nathan A. Smith1*, Qiwu Xu1, Takumi Fujita1, Akemichi Baba2, Toshio Matsuda3, Takahiro Takano1, Lane Bekar1, and Maiken Nedergaard1{dagger}

1 Division of Glia Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical School, Rochester, NY 14640, USA.
2 School of Pharmacy, Hyogo University of Health Sciences, Kobe, Hyogo 650-8530, Japan.
3 Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.

* These authors contributed equally to this work.

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.

{dagger} To whom correspondence should be addressed. E-mail: nedergaard{at}urmc.rochester.edu

Citation: F. Wang, N. A. Smith, Q. Xu, T. Fujita, A. Baba, T. Matsuda, T. Takano, L. Bekar, M. Nedergaard, Astrocytes Modulate Neural Network Activity by Ca2+-Dependent Uptake of Extracellular K+. Sci. Signal. 5, ra26 (2012).

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