Astrocyte calcium elevations: Properties, propagation, and effects on brain signaling

Abstract

The possibility that astrocytes are involved in brain signaling began to emerge in the late 1970s, when it was first shown that astroglia in vitro possess numerous receptors for neurotransmitters. It was later demonstrated that cultured astroglia and astrocytes in situ respond to neurotransmitters with increases in intracellular second messengers, including cyclic AMP and calcium. Astrocyte calcium responses have since been extensively studied both in culture and in intact tissue. We continue to gather information regarding the various compounds able to trigger astrocyte calcium increases, as well as the mechanisms involved in their initiation, propagation as a calcium wave within and between astrocytes, and effects on signaling within the brain. This review will focus on each of these aspects of astrocyte calcium regulation, and attempt to sort out which effects are more likely to occur in developmental, pathological, and physiological conditions. While we have come far in our understanding of the properties or potential of astrocytes' ability to signal to neurons using our array of pharmacological tools, we still understand very little regarding the level of involvement of astrocyte signaling in normal brain physiology.

Loss of IP3Receptor-Dependent Ca2+Increases in Hippocampal Astrocytes Does Not Affect Baseline CA1 Pyramidal Neuron Synaptic Activity

“…A substantial literature has developed in the field of astrocyte biology concerning the role of Ca 2ϩ -dependent release of gliotransmitters such as ATP (which is converted to adenosine by ectonucleotidases) and glutamate on neuronal activity (for review, see Carmignoto and Fellin, 2006;Fellin et al, 2006b;Fiacco and McCarthy, 2006). These findings led to the development of the tripartite synapse model, in which astrocytes are active participants in synaptic transmission through Ca 2ϩ -dependent gliotransmitter release (Araque et al, 1999).…”

Peptidylarginine deiminase and protein citrullination in prion diseases

“…This release can be a response to neuronal activity, and can also be propagated through Ca 2+ signaling from neighboring astrocytes through various mechanisms involving a number of channels and receptors such as voltage-gated Ca 2+ channels, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, N-methyl-d-aspartate receptors, and ionotropic glutamate and purine receptors. [48][49][50] Astrocyte-released gliotransmitters connect astrocytes with neurons and other astrocytes for neuronal communication and are typically induced by Ca 2+ signaling. Moreover, Ca 2+ may play a regulatory role in PAD2 transcription.…”

Astrocytes Control Glutamate Receptor Levels at Developing Synapses through SPARC–β-Integrin Interactions

“…Glutamate, in particular, is well known to trigger intracellular signals in astrocytes (Fiacco and McCarthy, 2006). To determine whether SPARC expression could be influenced by glutamate, we treated dissociated hippocampal astrocytes with glutamate (20 M for 6 h) and assessed the level of SPARC protein.…”