ATP release by way of connexin 36 hemichannels mediates ischemic tolerance in vitro

Schock, Sarah C.; Leblanc, Danielle; Hakim, Antoine M.; Thompson, C. S.

doi:10.1016/j.bbrc.2008.01.054

Cited by 110 publications

(100 citation statements)

References 32 publications

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“…The surface increase of Cx43 in astrocytes and Cx43/Panx1 in microglia is likely enough to account for the observed increase in hemichannel activity. In neurons, Cx36 or Panx1 were detected as previously reported (Huang et al, 2007;Schock et al, 2008); however, only changes in Panx1 surface levels were observed. Alternatively, the increase in hemichannel activity might be explained by enhanced open probability or channel permeability resulting from covalent modifications (e.g., phosphorylation and/or S-nitrosylation).…”

Section: Discussionsupporting

confidence: 79%

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Amyloid β-Induced Death in Neurons Involves Glial and Neuronal Hemichannels

et al. 2011

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The mechanisms involved in Alzheimer's disease are not completely understood and how glial cells contribute to this neurodegenerative disease remains to be elucidated. Because inflammatory treatments and products released from activated microglia increase glial hemichannel activity, we investigated whether amyloid-␤ peptide (A␤) could regulate these channels in glial cells and affect neuronal viability. Microglia, astrocytes, or neuronal cultures as well as acute hippocampal slices made from GFAP-eGFP transgenic mice were treated with the active fragment of A␤. Hemichannel activity was monitored by single-channel recordings and by time-lapse ethidium uptake, whereas neuronal death was assessed by Fluoro-Jade C staining. We report that low concentrations of A␤ 25-35 increased hemichannel activity in all three cell types and microglia initiate these effects triggered by A␤. Finally, neuronal damage occurs by activation of neuronal hemichannels induced by ATP and glutamate released from A␤ 25-35 -activated glia. These responses were observed in the presence of external calcium and were differently inhibited by hemichannel blockers, whereas the A␤ 25-35 -induced neuronal damage was importantly reduced in acute slices made from Cx43 knock-out mice. Thus, A␤ leads to a cascade of hemichannel activation in which microglia promote the release of glutamate and ATP through glial (microglia and astrocytes) hemichannels that induces neuronal death by triggering hemichannels in neurons. Consequently, this work opens novel avenues for alternative treatments that target glial cells and neurons to maintain neuronal survival in the presence of A␤.

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Section: Discussionsupporting

confidence: 79%

“…Since Cx36 and Panx1 have been detected in neurons (Huang et al, 2007;Schock et al, 2008), we investigated their expression levels in neurons. Total and surface Cx36 levels in neurons under control conditions or those subjected to A␤ 25-35 treatment were similar (Fig.…”

Section: Cultured Microglia Astrocytes and Neurons Treated With A␤ mentioning

confidence: 99%

Amyloid β-Induced Death in Neurons Involves Glial and Neuronal Hemichannels

et al. 2011

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“…Both ATP release and Ca 2+ wave propagation were markedly reduced by Cx40 siRNA, suggesting that interendothelial calcium signaling in the juxtaglomerular vasculature is mediated by Cx40-dependent ATP release and subsequent activation of purinergic receptors [123]. ATP release from cerebellar granule neurons exposed to depolarizing conditions was reduced after knocking down connexin 36 expression via siRNA [124].…”

Section: Connexinsmentioning

confidence: 98%

Vesicular and conductive mechanisms of nucleotide release

Lazarowski

2012

Purinergic Signalling

254

225

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Extracellular nucleotides and nucleosides promote a vast range of physiological responses, via activation of cell surface purinergic receptors. Virtually all tissues and cell types exhibit regulated release of ATP, which, in many cases, is accompanied by the release of uridine nucleotides. Given the relevance of extracellular nucleotide/nucleoside-evoked responses, understanding how ATP and other nucleotides are released from cells is an important physiological question. By facilitating the entry of cytosolic nucleotides into the secretory pathway, recently identified vesicular nucleotide and nucleotide-sugar transporters contribute to the exocytotic release of ATP and UDP-sugars not only from endocrine/exocrine tissues, but also from cell types in which secretory granules have not been biochemically characterized. In addition, plasma membrane connexin hemichannels, pannexin channels, and less-well molecularly defined ATP conducting anion channels have been shown to contribute to the release of ATP (and UTP) under a variety of conditions.

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“…28 This interesting study requires confirmation by other techniques, such as electrophysiological demonstration of Cx36 hemichannels and determination if these hemichannels are in interneurons or pyramidal neurons in the cultures. Interneurons express Cx36 into the adult but Cx36 mediated gap junctions between pyramidal neurons of the neocortex are only observed until postnatal day 12.…”

Section: Hemichannel Definedmentioning

confidence: 99%

Connexin and pannexin hemichannels of neurons and astrocytes

Thompson

MacVicar²

2008

Channels

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Hemichannels are large pore ion channels that in the traditional view are formed when half a gap connexin junction opens to the extracellular space. It is now evident that other ion channel families, including the newly discovered pannexin family can form channels with all the nascent properties of hemichannels. This suggests that hemichannels should now be defined to include members of non-connexin families. Several connexin, and two pannexins are expressed in neurons and astrocytes where they may function in release of ATP and glutamate. Additionally, pannexin-1 appears to play a role in neuronal death. Hemichannels form a novel and unique class of ion channels that likely have diverse physiological and pathophysiological roles in the nervous system.

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ATP release by way of connexin 36 hemichannels mediates ischemic tolerance in vitro

Cited by 110 publications

References 32 publications

Amyloid β-Induced Death in Neurons Involves Glial and Neuronal Hemichannels

Amyloid β-Induced Death in Neurons Involves Glial and Neuronal Hemichannels

Vesicular and conductive mechanisms of nucleotide release

Connexin and pannexin hemichannels of neurons and astrocytes

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