Intercellular Calcium Signaling in Astrocytes via ATP Release through Connexin Hemichannels

Stout, Charles; Costantin, James L.; Naus, Christian C.; Charles, Andrew

doi:10.1074/jbc.m109902200

Cited by 797 publications

(763 citation statements)

References 32 publications

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“…We and others have recently provided evidence for a mechanism that reconciles roles for both connexins and ATP release in astrocyte Ca 2ϩ signaling, i.e., release of ATP through connexin hemichannels (Cotrina et al, 1998;Stout et al, 2002). In this study, we provide evidence that extracellular Ca 2ϩ and Mg 2ϩ modulate Ca 2ϩ signaling in astrocytes through their influence on this novel signaling pathway.…”

Section: Introductionsupporting

confidence: 57%

“…The sample size for each treatment or control was eight plates, with most experiments being repeated three different times. Calcein blue release assays were performed as previously described (Stout et al, 2002), by loading cells with Calcein Blue AM (10 M for 30 minutes) prior to stimulation and measuring dye release into the medium and in cell lysates with a fluorescence plate reader.…”

Section: Mass Mechanical Stimulation and Collection Of Extracellular mentioning

confidence: 99%

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Modulation of intercellular calcium signaling in astrocytes by extracellular calcium and magnesium

Stout

Charles

2003

Glia

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The extracellular concentrations of Ca 2ϩ and Mg 2ϩ are well known to play important roles in the function of the central nervous system. We examined the effects of extracellular Ca 2ϩ and Mg 2ϩ on ATP release and intercellular signaling in astrocytes. [Ca 2ϩ ] o -activated whole cell currents consistent with currents through connexin hemichannels. These currents were inhibited by extracellular Mg 2ϩ . We conclude that extracellular divalent cations modulate intercellular Ca 2ϩ signaling in astrocytes by modulating the release of ATP, possibly via connexin hemichannels.

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Section: Introductionsupporting

confidence: 57%

Section: Mass Mechanical Stimulation and Collection Of Extracellular mentioning

confidence: 99%

Modulation of intercellular calcium signaling in astrocytes by extracellular calcium and magnesium

Stout

Charles

2003

Glia

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“…ATP is released from cells through various mechanisms, including exocytosis [34], maxi-anion channels [35], volumesensitive outwardly rectifying chloride channels [36], and gap-junction hemichannels [37]. Although the mechanism of release of ATP from cancer cells has not been clearly established, it is possible that the ability to release ATP is correlated with malignancy or motility of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Autocrine signaling via release of ATP and activation of P2X7 receptor influences motile activity of human lung cancer cells

Takai

Tsukimoto

Hishida

et al. 2014

Purinergic Signalling

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Extracellular nucleotides, such as ATP, are released from cells and play roles in various physiological and pathological processes through activation of P2 receptors. Here, we show that autocrine signaling through release of ATP and activation of P2X7 receptor influences migration of human lung cancer cells. Release of ATP was induced by stimulation with TGF-β1, which is a potent inducer of cell migration, in human lung cancer H292 cells, but not in noncancerous BEAS-2B cells. Treatment of H292 cells with a specific antagonist of P2X7 receptor resulted in suppression of TGF-β1-induced migration. PC-9 human lung cancer cells released a large amount of ATP under standard cell culture conditions, and P2X7 receptor-dependent dye uptake was observed even in the absence of exogenous ligand, suggesting constitutive activation of P2X7 receptor in this cell line. PC-9 cells showed high motile activity, which was inhibited by treatment with ecto-nucleotidase and P2X7 receptor antagonists, whereas a P2X7 receptor agonist enhanced migration. PC-9 cells also harbor a constitutively active mutation in epidermal growth factor receptor (EGFR). Treatment with EGFR tyrosine kinase inhibitor AG1478 suppressed both cell migration and P2X7 receptor expression in PC-9 cells. Compared to control PC-9 cells, cells treated with P2X7 antagonist exhibited broadened lamellipodia around the cell periphery, while AG1478-treated cells lacked lamellipodia. These results indicate that P2X7-mediated signaling and EGFR signaling may regulate migration of PC-9 cells through distinct mechanisms. We propose that autocrine ATP-P2X7 signaling is involved in migration of human lung cancer cells through regulation of actin cytoskeleton rearrangement.

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“…Ca 2+ oscillations have been reported in a great variety of non-excitable cells including pancreatic β-cells [49], embryonic stem cells (ESCs) [47], chondroblasts [11,35], chondrocytes [40] and human MSCs [22,24]. This is the first study to report that human chondroprogenitor cells derived from regions with minor lesions of osteoarthritic articular cartilage (CPCs) are also characterised by a similarly dynamic Ca 2+ homeostasis.…”

Section: Dynamics Of Cytosolic [Ca 2+ ]Imentioning

confidence: 96%

Purinergic signalling is required for calcium oscillations in migratory chondrogenic progenitor cells

Matta

Fodor

Miosge

et al. 2014

Pflugers Arch - Eur J Physiol

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Osteoarthritis (OA) is the most common form of chronic musculoskeletal disorders. A migratory stem cell population termed chondrogenic progenitor cells (CPC) with in vitro chondrogenic potential was previously isolated from OA cartilage. Since intracellular Ca 2+ signalling is an important regulator of chondrogenesis, we aimed to provide a detailed understanding of the Ca 2+ homeostasis of CPCs. In this work, CPCs immortalised by lentiviral administration of the human telomerase reverse transcriptase (hTERT) and grown in monolayer cultures were studied. Expressions of all three IP3Rs were confirmed, but no RyR subtypes were detected. Ca 2+ oscillations observed in CPCs were predominantly dependent on Ca 2+ release and store replenishment via store-operated Ca 2+ entry; CPCs express both STIM1 and Orai1 proteins. Expressions of adenosine receptor mRNAs were verified, and adenosine elicited Ca 2+ transients. Various P2 receptor subtypes were identified; P2Y1 can bind ADP; P2Y4 is targeted by UTP; and ATP may evoke Ca 2+ transients via detected P2X subtypes, as well as P2Y1 and P2Y2. Enzymatic breakdown of extracellular nucleotides by apyrase completely abrogated Ca 2+ oscillations, suggesting that an autocrine/paracrine purinergic mechanism may drive Ca 2+ oscillations in these cells.As CPCs possess a broad spectrum of functional molecular elements of Ca 2+ signalling, Ca 2+ -dependent regulatory mechanisms can be supposed to influence their differentiation potential.

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Intercellular Calcium Signaling in Astrocytes via ATP Release through Connexin Hemichannels

Cited by 797 publications

References 32 publications

Modulation of intercellular calcium signaling in astrocytes by extracellular calcium and magnesium

Modulation of intercellular calcium signaling in astrocytes by extracellular calcium and magnesium

Autocrine signaling via release of ATP and activation of P2X7 receptor influences motile activity of human lung cancer cells

Purinergic signalling is required for calcium oscillations in migratory chondrogenic progenitor cells

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