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Review
. 2021 Oct 6;11(10):1467.
doi: 10.3390/biom11101467.

Extracellular Calcium Influx Pathways in Astrocyte Calcium Microdomain Physiology

Noushin Ahmadpour  1 , Meher Kantroo  1 , Jillian L Stobart  1
Affiliations
Review

Extracellular Calcium Influx Pathways in Astrocyte Calcium Microdomain Physiology

Noushin Ahmadpour et al. Biomolecules. .

Abstract

Astrocytes are complex glial cells that play many essential roles in the brain, including the fine-tuning of synaptic activity and blood flow. These roles are linked to fluctuations in intracellular Ca2+ within astrocytes. Recent advances in imaging techniques have identified localized Ca2+ transients within the fine processes of the astrocytic structure, which we term microdomain Ca2+ events. These Ca2+ transients are very diverse and occur under different conditions, including in the presence or absence of surrounding circuit activity. This complexity suggests that different signalling mechanisms mediate microdomain events which may then encode specific astrocyte functions from the modulation of synapses up to brain circuits and behaviour. Several recent studies have shown that a subset of astrocyte microdomain Ca2+ events occur rapidly following local neuronal circuit activity. In this review, we consider the physiological relevance of microdomain astrocyte Ca2+ signalling within brain circuits and outline possible pathways of extracellular Ca2+ influx through ionotropic receptors and other Ca2+ ion channels, which may contribute to astrocyte microdomain events with potentially fast dynamics.

Keywords: Ca2+ channels; Ca2+ transients; astrocytes; gliotransmission; ion influx; ionotropic receptors; sodium-calcium exchanger.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Examples of functional roles of astrocyte Ca2+ events. MCEs lead to gliotransmission: (1) ATP/adenosine a. downregulates the excitatory activity by activating presynaptic A1R [60] and b. upregulates inhibitory activity by activating postsynaptic A1R [40]. (2) D-serine enhances LTP via postsynaptic NMDARs [41]. (3) Glutamate released from astrocytes modulates pre- and post-synaptic neuronal glutamate receptors [36,50,56,57,59,61]. (4) In astrocyte endfeet, MCEs cause the production of arachidonic acid (AA) that is metabolized to vasodilative components, such as prostaglandins, and contribute to regulation of cerebral blood flow [12].
Figure 2
Figure 2
Astrocyte Ca2+ pathways activated during synaptic transmission. This diagram highlights the pathways that involve extracellular Ca2+ influx as discussed in this review.
Figure 3
Figure 3
Functional implications of astrocyte NMDA receptors. The following may occur as a result of Antioxidant protection NMDAR activity, possibly via astrocyte calcium events: (1) Modulation of synaptic activity; ATP gliotransmission is evoked that acts on presynaptic P2XRs and thus downregulates inhibitory activity [130]. (2) Regulation of synaptic strength: reduced astrocyte NMDAR expression decreases the paired-pulse ratio variability [49,139] (3) Protection of neurons against antioxidant stress; NMDAR activation upregulates expression of cdk5/p35 that promotes expression of glutathione precursors through Nrf2 [121]. (4) Regulation of basal astrocyte Ca2+ concentrations, which can define MCEs characteristics such as amplitude and peak frequency [26,27].
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