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

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.