Activation of the TRPV1 cation channel contributes to stress-induced astrocyte migration.

Ho KW, Lambert WS, Calkins DJ
Glia. 2014 62 (9): 1435-51

PMID: 24838827 · PMCID: PMC4107153 · DOI:10.1002/glia.22691

Astrocytes provide metabolic, structural, and synaptic support to neurons in normal physiology and also contribute widely to pathogenic processes in response to stress or injury. Reactive astrocytes can undergo cytoskeletal reorganization and increase migration through changes in intracellular Ca(2+) mediated by a variety of potential modulators. Here we tested whether migration of isolated retinal astrocytes following mechanical injury (scratch wound) involves the transient receptor potential vanilloid-1 channel (TRPV1), which contributes to Ca(2+)-mediated cytoskeletal rearrangement and migration in other systems. Application of the TRPV1-specific antagonists, capsazepine (CPZ) or 5'-iodoresiniferatoxin (IRTX), slowed migration by as much as 44%, depending on concentration. In contrast, treatment with the TRPV1-specific agonists, capsaicin (CAP) or resiniferatoxin (RTX) produced only a slight acceleration over a range of concentrations. Chelation of extracellular Ca(2+) with EGTA (1 mM) slowed astrocyte migration by 35%. Ratiometric imaging indicated that scratch wound induced a sharp 20% rise in astrocyte Ca(2+) that dissipated with distance from the wound. Treatment with IRTX both slowed and dramatically reduced the scratch-induced Ca(2+) increase. Both CPZ and IRTX influenced astrocyte cytoskeletal organization, especially near the wound edge. Taken together, our results indicate that astrocyte mobilization in response to mechanical stress involves influx of extracellular Ca(2+) and cytoskeletal changes in part mediated by TRPV1 activation.

© 2014 Wiley Periodicals, Inc.

MeSH Terms (14)

Animals Astrocytes Calcium Cell Culture Techniques Cell Movement Cells, Cultured Cytoskeleton Extracellular Space Intracellular Space Mice, Inbred C57BL Rats, Sprague-Dawley Retina Stress, Mechanical TRPV Cation Channels

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