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

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 ce...

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Autores principales:	E. Murana, F. Pagani, B. Basilico, M. Sundukova, L. Batti, S. Di Angelantonio, B. Cortese, A. Grimaldi, A. Francioso, P. Heppenstall, P. Bregestovski, C. Limatola, D. Ragozzino
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d77ebf08d06c4d1b83ceb109bfaf6f96
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spelling	oai:doaj.org-article:d77ebf08d06c4d1b83ceb109bfaf6f962021-12-02T16:06:10ZATP release during cell swelling activates a Ca2+-dependent Cl− current by autocrine mechanism in mouse hippocampal microglia10.1038/s41598-017-04452-82045-2322https://doaj.org/article/d77ebf08d06c4d1b83ceb109bfaf6f962017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04452-8https://doaj.org/toc/2045-2322Abstract 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.E. MuranaF. PaganiB. BasilicoM. SundukovaL. BattiS. Di AngelantonioB. CorteseA. GrimaldiA. FranciosoP. HeppenstallP. BregestovskiC. LimatolaD. RagozzinoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q E. Murana F. Pagani B. Basilico M. Sundukova L. Batti S. Di Angelantonio B. Cortese A. Grimaldi A. Francioso P. Heppenstall P. Bregestovski C. Limatola D. Ragozzino ATP release during cell swelling activates a Ca2+-dependent Cl− current by autocrine mechanism in mouse hippocampal microglia
description	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.
format	article
author	E. Murana F. Pagani B. Basilico M. Sundukova L. Batti S. Di Angelantonio B. Cortese A. Grimaldi A. Francioso P. Heppenstall P. Bregestovski C. Limatola D. Ragozzino
author_facet	E. Murana F. Pagani B. Basilico M. Sundukova L. Batti S. Di Angelantonio B. Cortese A. Grimaldi A. Francioso P. Heppenstall P. Bregestovski C. Limatola D. Ragozzino
author_sort	E. Murana
title	ATP release during cell swelling activates a Ca2+-dependent Cl− current by autocrine mechanism in mouse hippocampal microglia
title_short	ATP release during cell swelling activates a Ca2+-dependent Cl− current by autocrine mechanism in mouse hippocampal microglia
title_full	ATP release during cell swelling activates a Ca2+-dependent Cl− current by autocrine mechanism in mouse hippocampal microglia
title_fullStr	ATP release during cell swelling activates a Ca2+-dependent Cl− current by autocrine mechanism in mouse hippocampal microglia
title_full_unstemmed	ATP release during cell swelling activates a Ca2+-dependent Cl− current by autocrine mechanism in mouse hippocampal microglia
title_sort	atp release during cell swelling activates a ca2+-dependent cl− current by autocrine mechanism in mouse hippocampal microglia
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d77ebf08d06c4d1b83ceb109bfaf6f96
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ATP release during cell swelling activates a Ca2+-dependent Cl− current by autocrine mechanism in mouse hippocampal microglia

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