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Journal Articles Frontiers in Cellular Neuroscience Year : 2021

Astrocytic IP3Rs: Beyond IP3R2


Astrocytes are sensitive to ongoing neuronal/network activities and, accordingly, regulate neuronal functions (synaptic transmission, synaptic plasticity, behavior, etc.) by the context-dependent release of several gliotransmitters (e.g., glutamate, glycine, D -serine, ATP). To sense diverse input, astrocytes express a plethora of G-protein coupled receptors, which couple, via G i/o and G q , to the intracellular Ca 2+ release channel IP 3 -receptor (IP 3 R). Indeed, manipulating astrocytic IP 3 R-Ca 2+ signaling is highly consequential at the network and behavioral level: Depleting IP 3 R subtype 2 (IP 3 R2) results in reduced GPCR-Ca 2+ signaling and impaired synaptic plasticity; enhancing IP 3 R-Ca 2+ signaling affects cognitive functions such as learning and memory, sleep, and mood. However, as a result of discrepancies in the literature, the role of GPCR-IP 3 R-Ca 2+ signaling, especially under physiological conditions, remains inconclusive. One primary reason for this could be that IP 3 R2 has been used to represent all astrocytic IP 3 Rs, including IP 3 R1 and IP 3 R3. Indeed, IP 3 R1 and IP 3 R3 are unique Ca 2+ channels in their own right; they have unique biophysical properties, often display distinct distribution, and are differentially regulated. As a result, they mediate different physiological roles to IP 3 R2. Thus, these additional channels promise to enrich the diversity of spatiotemporal Ca 2+ dynamics and provide unique opportunities for integrating neuronal input and modulating astrocyte–neuron communication. The current review weighs evidence supporting the existence of multiple astrocytic-IP 3 R isoforms, summarizes distinct sub-type specific properties that shape spatiotemporal Ca 2+ dynamics. We also discuss existing experimental tools and future refinements to better recapitulate the endogenous activities of each IP 3 R isoform.

Dates and versions

hal-03372662 , version 1 (11-10-2021)



Mark Sherwood, Misa Arizono, Aude Panatier, Katsuhiko Mikoshiba, Stéphane Oliet. Astrocytic IP3Rs: Beyond IP3R2. Frontiers in Cellular Neuroscience, 2021, 15, ⟨10.3389/fncel.2021.695817⟩. ⟨hal-03372662⟩
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