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Elke De Vuyst Nan Wang Elke Decrock Marijke De Bock Mathieu Vinken Marijke Van Moorhem Charles Lai Maxime Culot Vera Rogiers Romeo Cecchelli Christian C. Naus W. Howard Evans Luc Leybaert 《Cell calcium》2009,46(3):176-187
Connexin hemichannels have a low open probability under normal conditions but open in response to various stimuli, forming a release pathway for small paracrine messengers. We investigated hemichannel-mediated ATP responses triggered by changes of intracellular Ca2+ ([Ca2+]i) in Cx43 expressing glioma cells and primary glial cells. The involvement of hemichannels was confirmed with gja1 gene-silencing and exclusion of other release mechanisms. Hemichannel responses were triggered when [Ca2+]i was in the 500 nM range but the responses disappeared with larger [Ca2+]i transients. Ca2+-triggered responses induced by A23187 and glutamate activated a signaling cascade that involved calmodulin (CaM), CaM-dependent kinase II, p38 mitogen activated kinase, phospholipase A2, arachidonic acid (AA), lipoxygenases, cyclo-oxygenases, reactive oxygen species, nitric oxide and depolarization. Hemichannel responses were also triggered by activation of CaM with a Ca2+-like peptide or exogenous application of AA, and the cascade was furthermore operational in primary glial cells isolated from rat cortex. In addition, several positive feed-back loops contributed to amplify the responses. We conclude that an elevation of [Ca2+]i triggers hemichannel opening, not by a direct action of Ca2+ on hemichannels but via multiple intermediate signaling steps that are adjoined by distinct signaling mechanisms activated by high [Ca2+]i and acting to restrain cellular ATP loss. 相似文献
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Shohei Segawa Takeshi NishiuraTakahiro Furuta Yuki OhsatoMisaki Tani Kentaro NishidaKazuki Nagasawa 《Life sciences》2014
Aim
Astrocytes contribute to the maintenance of brain homeostasis via the release of gliotransmitters such as ATP and glutamate. Here we examined whether zinc was released from astrocytes under stress-loaded conditions, and was involved in the regulation of microglial activity as a gliotransmitter.Main methods
Hypoosmotic stress was loaded to astrocytes using balanced salt solution prepared to 214–314 mOsmol/L, and then intra- and extra-cellular zinc levels were assessed using Newport Green DCF diacetate (NG) and ICP-MS, respectively. Microglial activation by the astrocytic supernatant was assessed by their morphological changes and poly(ADP-ribose) (PAR) polymer accumulation.Key findings
Exposure of astrocytes to hypoosmotic buffer, increased the extracellular ATP level in osmolarity-dependent manners, indicating a load of hypoosmotic stress. In hypoosmotic stress-loaded astrocytes, there were apparent increases in the intra- and extra-cellular zinc levels. Incubation of microglia in the astrocytic conditioned medium transformed them into the activated “amoeboid” form and induced PAR formation. Administration of an extracellular zinc chelator, CaEDTA, to the astrocytic conditioned medium almost completely prevented the microglial activation. Treatment of astrocytes with an intracellular zinc chelator, TPEN, suppressed the hypoosmotic stress-increased intracellular, but not the extracellular, zinc level, and the increase in the intracellular zinc level was blocked partially by a nitric oxide synthase inhibitor, but not by CaEDTA, indicating that the mechanisms underlying the increases in the intra- and extra-cellular zinc levels might be different.Significance
These findings suggest that under hypoosmotic stress-loaded conditions, zinc is released from astrocytes and then plays a primary role in microglial activation as a gliotransmitter. 相似文献3.
Koji Shibasaki Kazuhiro Ikenaka Fuminobu Tamalu Makoto Tominaga Yasuki Ishizaki 《The Journal of biological chemistry》2014,289(21):14470-14480
Astrocytes play active roles in the regulation of synaptic transmission. Neuronal excitation can evoke Ca2+ transients in astrocytes, and these Ca2+ transients can modulate neuronal excitability. Although only a subset of astrocytes appears to communicate with neurons, the types of astrocytes that can regulate neuronal excitability are poorly characterized. We found that ∼30% of astrocytes in the brain express transient receptor potential vanilloid 4 (TRPV4), indicating that astrocytic subtypes can be classified on the basis of their expression patterns. When TRPV4+ astrocytes are activated by ligands such as arachidonic acid, the activation propagates to neighboring astrocytes through gap junctions and by ATP release from the TRPV4+ astrocytes. After activation, both TRPV4+ and TRPV4− astrocytes release glutamate, which acts as an excitatory gliotransmitter to increase synaptic transmission through type 1 metabotropic glutamate receptor (mGluR). Our results indicate that TRPV4+ astrocytes constitute a novel subtype of the population and are solely responsible for initiating excitatory gliotransmitter release to enhance synaptic transmission. We propose that TRPV4+ astrocytes form a core of excitatory glial assembly in the brain and function to efficiently increase neuronal excitation in response to endogenous TRPV4 ligands. 相似文献
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Metabotropic Glutamate Receptors in Glial Cells 总被引:1,自引:1,他引:0
D'Antoni S Berretta A Bonaccorso CM Bruno V Aronica E Nicoletti F Catania MV 《Neurochemical research》2008,33(12):2436-2443
Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS) and exerts its actions via
a number of ionotropic glutamate receptors/channels and metabotropic glutamate (mGlu) receptors. In addition to being expressed
in neurons, glutamate receptors are expressed in different types of glial cells including astrocytes, oligodendrocytes, and
microglia. Astrocytes are now recognized as dynamic signaling elements actively integrating neuronal inputs. Synaptic activity
can evoke calcium signals in astrocytes, resulting in the release of gliotransmitters, such as glutamate, ATP, and d-serine, which in turn modulate neuronal excitability and synaptic transmission. In addition, astrocytes, and microglia may
play an important role in pathology such as brain trauma and neurodegeneration, limiting or amplifying the pathologic process
leading to neuronal death. The present review will focus on recent advances on the role of mGlu receptors expressed in glial
cells under physiologic and pathologic conditions.
Special issue article in honor of Dr. Anna Maria Giuffrida-Stella. 相似文献
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