Astrocyte calcium waves: what they are and what they do

Abstract

Several lines of evidence indicate that the elaborated calcium signals and the occurrence of calcium waves in astrocytes provide these cells with a specific form of excitability. The identification of the cellular and molecular steps involved in the triggering and transmission of Ca(2+) waves between astrocytes resulted in the identification of two pathways mediating this form of intercellular communication. One of them involves the direct communication between the cytosols of two adjoining cells through gap junction channels, while the other depends upon the release of "gliotransmitters" that activates membrane receptors on neighboring cells. In this review we summarize evidence in favor of these two mechanisms of Ca(2+) wave transmission and we discuss that they may not be mutually exclusive, but are likely to work in conjunction to coordinate the activity of a group of cells. To address a key question regarding the functional consequences following the passage of a Ca(2+) wave, we list, in this review, some of the potential intracellular targets of these Ca(2+) transients in astrocytes, and discuss the functional consequences of the activation of these targets for the interactions that astrocytes maintain with themselves and with other cellular partners, including those at the glial/vasculature interface and at perisynaptic sites where astrocytic processes tightly interact with neurons.

Fig. 1

Intercellular Ca²⁺ waves and their intracellular targets. (A) The transmission of intercellular Ca²⁺ signals between astrocytes is illustrated in the sequential images obtained from Fluo-3-AM loaded spinal cord astrocytes. Mechanical stimulation (arrow) of a single astrocyte in culture induces intracellular Ca²⁺ elevation (displayed as an increase in fluorescence intensity) in the stimulated cells, which is then followed by Ca²⁺ increases in neighboring astrocytes. Images were acquired with an Orca-ER CCD camara attached to Nikon TE2000 inverted microscope equipped with a ×10 objective, using Metafluor software. Bar: 50 μm. (B) The diagram illustrates the major intracellular targets of cytosolic Ca²⁺ fluctuations in astrocytes. Elevation of intracellular Ca²⁺ levels is shown to affect (arrows) several plasma membrane proteins (symbols refer from left to right to metabotropic receptors, K⁺ (Ca²⁺) channels, Na⁺/Ca²⁺ exchanger, and Ca²⁺-ATPase), as well as intracellular ones. The inositol-trisphosphate receptors (IP₃R) are located at the endoplasmic reticulum (ER) where Ca²⁺ exert a cooperative action. Rises in [Ca²⁺]_i also target several cytoskeleton elements (cytosk), enzymes (E), and vesicles involved on the release of “gliotransmitters”. Finally, Ca²⁺ and the Ca²⁺ liberating second messenger IP₃ permeate gap junction channels and then act on similar intracellular targets in neighboring coupled cells.