Microglia cells, resident immune cells of the brain, survey brain parenchyma by dynamically extending and retracting their processes. Cl- channels, activated in the cellular response to stretch/swelling, take part in several functions deeply connected with microglia physiology, including cell shape changes, proliferation, differentiation and migration. However, the molecular identity and functional properties of these Cl- channels are largely unknown. We investigated the properties of swelling-activated currents in microglial from acute hippocampal slices of Cx3cr1+/GFP mice by whole-cell patch-clamp and imaging techniques. The exposure of cells to a mild hypotonic medium, caused an outward rectifying current, developing in 5-10 minutes and reverting upon stimulus washout. This current, required for microglia ability to extend processes towards a damage signal, was carried mainly by Cl- ions and dependent on intracellular Ca2+. Moreover, it involved swelling-induced ATP release. We identified a purine-dependent mechanism, likely constituting an amplification pathway of current activation: under hypotonic conditions, ATP release triggered the Ca2+-dependent activation of anionic channels by autocrine purine receptors stimulation. Our study on native microglia describes for the first time the functional properties of stretch/swelling-activated currents, representing a key element in microglia ability to monitor the brain parenchyma.

ATP release during cell swelling activates a Ca2+-dependent Cl - Current by autocrine mechanism in mouse hippocampal microglia / Murana, E.; Pagani, F.; Basilico, B.; Sundukova, M.; Batti, L.; Di Angelantonio, S.; Cortese, B.; Grimaldi, A.; Francioso, A.; Heppenstall, P.; Bregestovski, P.; Limatola, C.; Ragozzino, D.. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 7:1(2017), pp. 1-16. [10.1038/s41598-017-04452-8]

ATP release during cell swelling activates a Ca2+-dependent Cl - Current by autocrine mechanism in mouse hippocampal microglia

Sundukova, M.;Di Angelantonio, S.;Heppenstall, P.;
2017

Abstract

Microglia cells, resident immune cells of the brain, survey brain parenchyma by dynamically extending and retracting their processes. Cl- channels, activated in the cellular response to stretch/swelling, take part in several functions deeply connected with microglia physiology, including cell shape changes, proliferation, differentiation and migration. However, the molecular identity and functional properties of these Cl- channels are largely unknown. We investigated the properties of swelling-activated currents in microglial from acute hippocampal slices of Cx3cr1+/GFP mice by whole-cell patch-clamp and imaging techniques. The exposure of cells to a mild hypotonic medium, caused an outward rectifying current, developing in 5-10 minutes and reverting upon stimulus washout. This current, required for microglia ability to extend processes towards a damage signal, was carried mainly by Cl- ions and dependent on intracellular Ca2+. Moreover, it involved swelling-induced ATP release. We identified a purine-dependent mechanism, likely constituting an amplification pathway of current activation: under hypotonic conditions, ATP release triggered the Ca2+-dependent activation of anionic channels by autocrine purine receptors stimulation. Our study on native microglia describes for the first time the functional properties of stretch/swelling-activated currents, representing a key element in microglia ability to monitor the brain parenchyma.
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https://www.nature.com/articles/s41598-017-04452-8
Murana, E.; Pagani, F.; Basilico, B.; Sundukova, M.; Batti, L.; Di Angelantonio, S.; Cortese, B.; Grimaldi, A.; Francioso, A.; Heppenstall, P.; Bregestovski, P.; Limatola, C.; Ragozzino, D.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11767/87762
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