Astrocyte Ca2+-evoked ATP release regulates myelinated axon excitability and conduction speed

Jonathan Lezmy*, I. Lorena Arancibia-Cárcamo, Tania Quintela-López, Diane L. Sherman, Peter J. Brophy, David Attwell*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


In the brain's gray matter, astrocytes regulate synapse properties, but their role is unclear for the white matter, where myelinated axons rapidly transmit information between gray matter areas. We found that in rodents, neuronal activity raised the intracellular calcium concentration ([Ca2+]i) in astrocyte processes located near action potential-generating sites in the axon initial segment (AIS) and nodes of Ranvier of myelinated axons. This released adenosine triphosphate, which was converted extracellularly to adenosine and thus, through A2a receptors, activated HCN2-containing cation channels that regulate two aspects of myelinated axon function: excitability of the AIS and speed of action potential propagation. Variations in astrocyte-derived adenosine level between wake and sleep states or during energy deprivation could thus control white matter information flow and neural circuit function.

Original languageEnglish
Article numbereabh2858
Issue number6565
StatePublished - 15 Oct 2021
Externally publishedYes


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