Intercellular Calcium Signaling in Astrocytes via ATP Release through Connexin Hemichannels*

By Charles E Stout, J. Costantin, C. Naus, A. Charles. Journal of Biological Chemistry, 2002

896 citations recorded by the source corpus.

Astrocytes are capable of widespread intercellular communication via propagated increases in intracellular Ca2+ concentration. We have used patch clamp, dye flux, ATP assay, and Ca2+ imaging techniques to show that one mechanism for this intercellular Ca2+ signaling in astrocytes is the release of ATP through connexin channels (“hemichannels”) in individual cells. Astrocytes showed low Ca2+-activated whole-cell currents consistent with connexin hemichannel currents that were inhibited by the connexin channel inhibitor flufenamic acid (FFA). Astrocytes also showed molecular weight-specific influx and release of dyes, consistent with flux through connexin hemichannels. Transmembrane dye flux evoked by mechanical stimulation was potentiated by low Ca2+ and was inhibited by FFA and Gd3+. Mechanical stimulation also evoked release of ATP that was potentiated by low Ca2+ and inhibited by FFA and Gd3+. Similar whole-cell currents, transmembrane dye flux, and ATP release were observed in C6 glioma cells expressing connexin43 but were not observed in parent C6 cells. The connexin hemichannel activator quinine evoked ATP release and Ca2+ signaling in astrocytes and in C6 cells expressing connexin43. The propagation of intercellular Ca2+ waves in astrocytes was also potentiated by quinine and inhibited by FFA and Gd3+. Release of ATP through connexin hemichannels represents a novel signaling pathway for intercellular communication in astrocytes and other non-excitable cells.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/b756bf479268793398f71c84b39bc8e2b35758bb

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Citations in the corpus

Do astrocytes really exocytose neurotransmitters? (2010, background): “and have been shown to allow ATP and glutamate release from astrocytes in culture (and from white matter in vivo ) when activated in ischaemic condition”
Reading the patterns in living cells —the physics of ca2+ signaling (2004, background): “That creates the possibility that ATP is released through connexin hemichannels [495, 521, 522].”
Beyond the gap: functions of unpaired connexon channels (2003, background): “) and are repressed by the gap-junction blocker FF”
Astrocyte roles in traumatic brain injury (2015, background): “ATP is released via connexin hemi-channels, which are abundantly expressed by astrocytes (Rouach et al., 2002; Stout et al., 2002).”
Plasma membrane channels formed by connexins: their regulation and functions. (2003, background): “Closure of hemichannels has been observed after extracellular application of lanthanide cations, La(3) (99, 251, 280, 291), or Gd(3) (562), or treatment with gap junction channel blockers, such as octanol, heptanol, carbenoxolone, oleamide, halothane, and 18- - and 18- glycyrrhetinic acid.”
ATP released by astrocytes mediates glutamatergic activity-dependent heterosynaptic suppression. (2003, background): “The property of synaptic conCotrina et al., 1998, 2000; Stout et al., 2002).”
Physiology of Astroglia. (2018, neutral): “K -ATPase (also known as Nervana 2).”
ATP mediates rapid microglial response to local brain injury in vivo (2005, background): “It has been shown that ATP release from cultured astrocytes and glioma cell lines involves connexin hemichannel”
Functional Hemichannels in Astrocytes: A Novel Mechanism of Glutamate Release (2003, background): “It has been suggested, for example, that open hemichannels can mediate ATP release (Stout et al., 2002), which in turn may stimulate glutamate release from astrocytes (Jeremic et al.”
Astrocytes, from brain glue to communication elements: the revolution continues (2005, background): “The opening probability of the hemichannels, which is very low in astrocytes bathed in physiological media, increases significantly by reducing the concentrations of divalent cations, notably Ca 2+ , and is accompanied by the release of both AT”