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

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

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

  1. Fushun Wang1,*,
  2. Nathan A. Smith1,*,
  3. Qiwu Xu1,
  4. Takumi Fujita1,
  5. Akemichi Baba2,
  6. Toshio Matsuda3,
  7. Takahiro Takano1,
  8. Lane Bekar1, and
  9. Maiken Nedergaard1,
  1. 1Division of Glia Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical School, Rochester, NY 14640, USA.
  2. 2School of Pharmacy, Hyogo University of Health Sciences, Kobe, Hyogo 650-8530, Japan.
  3. 3Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
  1. To whom correspondence should be addressed. E-mail: nedergaard{at}
  • * These authors contributed equally to this work.


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.


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

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